The differential effect of cooling on the responses of splenic capsular and vascular smooth muscle to nerve stimulation and noradrenaline

The responses of the capsular and vascular smooth muscle of the dog's spleen to splenic nerve stimulation and to infused noradrenaline have been studied in the isolated, blood-perfused preparation at 37°C, at 27°C and again after rewarming to 37°C. It was found that cooling per se had no effect on perfusion pressure but reduced splenic arterial blood flow, and caused no appreciable alteration in spleen volume. The increase in splenic flow resistance in response to nerve stimulation and noradrenaline was significantly greater at 27°C than at 37°C, but the concomitant reduction in spleen volume was significantly reduced.The enhanced effect of splenic nerve stimulation and noradrenaline on splenic flow resistance is discussed in terms of the relative contributions of an increased smooth muscle response and increased blood viscosity. The different effects of cooling on the responses of splenic vascular and capsular smooth muscle to nerve stimulation and noradrenaline are discussed in the context of the effect of cooling on other vascular and non-vascular smooth muscle.This work was supported by a grant from the Medical Research Council     

Comparison of the effects of stimulation of the sympathetic vasomotor nerves and the adrenal medullary catecholamines on the hind limb blood vessels of the rabbit

1. The responses to sympathetic nerve stimulation and to the adrenal medullary hormones have been studied in the hind limb vascular beds of the anaesthetized rabbit.2. Simultaneous measurements of femoral arterial blood pressure and of femoral venous blood flow indicate that stimulation of the sympathetic nerves decreases the calculated vascular conductance in both the intact and skinned hind limbs. Evidence is presented to show that these changes are due to vasoconstriction.3. The vasoconstriction in both skin and muscle vascular beds reaches a maximum at frequencies of stimulation around 15 Hz. No vasodilatation is obtained at any frequency of stimulation.4. The rabbit adrenal gland secretes only adrenaline during splanchnic nerve stimulation at frequencies between 3 and 60 Hz. The amounts liberated from both glands over this frequency range are 25-500 ng.kg body wt.(-1) min(-1).5. Intravenous infusions of adrenaline in concentrations similar to those liberated by the adrenal glands during splanchnic nerve stimulation, and of noradrenaline, cause only vasoconstrictor responses in skin and muscle.6. Simultaneous stimulation of the sympathetic nerves to the hind limb and infusion of adrenaline in quantities that could be liberated by splanchnic nerve stimulation at equivalent frequencies shows that the vasoconstrictor effects exerted by the individual components are additive, though the effects produced by the direct sympathetic nerve supply overshadow those produced by the catecholamine.7. The results are discussed in the context of the possible vascular role of the adrenal medullary hormones in the rabbit.     

The effect of cooling on the responses of splenic capsular and vascular smooth muscle to nerve stimulation in the dog

Field stimulation of strips of canine splenic capsule and splenic artery suspended in an organ bath causes in both a contraction that is enhanced by cooling from 37°C to 27°C. This finding contrasts with that from the isolated perfused canine spleen in which cooling to 27°C enhanced the vascular response to splenic nerve stimulation but depressed the capsular response. The results of experiments to resolve the apparent discrepancy in the capsular smooth muscle response to stimulation indicate that the reduced response in the perfused spleen probably results from the capsular smooth muscle fibres being less optimally placed on their length: tension curve at 27°C when spleen volume is less. There is thus no need to postulate any fundamental difference in properties between the smooth muscles from the two intrasplenic distributions.     

Neuropeptide Y and differential sympathetic control of splenic blood flow and capacitance function in the pig and dog

The roles of different mediators in the sympathetic regulation of the pig and dog spleens were investigated using a preparation with intact vascular perfusion in vivo. Sympathetic nerve stimulation caused overflow of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline (NA), arterial vasoconstriction, increase in venous blood flow and haematocrit. The dog spleen responded to single impulse stimulation, whereas more prolonged stimulation was required to elicit vascular responses in the pig spleen. Furthermore, the maximal splenic capacitance response was about 10 times larger in the dog than in the pig. After depletion of neuronal NA content by reserpine combined with preganglionic denervation, about 70% of the splenic arterial vasoconstrictor responses in the dog and pig still remained at 5 Hz stimulation. Fifty per cent of the capacitance response evoked by nerve stimulation still remained in the pig while in the dog spleen the capacitance response was virtually abolished after reserpine. The stimulation-evoked overflow of NPY-LI in pig spleen was increased several fold after reserpine treatment as compared to controls reaching levels in the venous effluent where exogenous NPY evokes vasoconstriction. In the dog spleen, overflow of NPY-LI was only observed after reserpine. Administration of NA caused arterial vasoconstriction with an initial increase in venous blood flow while NPY mainly reduced arterial blood flow. It is concluded that NA is involved in both the splenic arterial vasoconstriction and the capacitance responses while a non-adrenergic splenic vasoconstriction at least in the pig may be mediated by NPY.     

Pancreatic polypeptide family (APP,BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to α-adrenoceptor blockade

Electrical stimulation of the cat cervical sympathetic trunk caused submandibular salivary secretion and vasoconstriction simultaneously with a contraction of the nictitating membrane. Following α- and β-adrenoceptor blockade by phentolamine or phenoxybenzamine combined with propranolol, the salivary response and the nictitating membrane contraction upon sympathetic stimulation were almost abolished. A considerable vasoconstrictor response (up to 40% of control) however still remained in the submandibular gland. This yasoconstriction, which persisted after α-adrenoceptor blockade, was rather slow in onset and had a long duration without any poststimulatory hyperemia. Local intra-arterial infusions of noradrenaline caused submandibular vasoconstriction, salivary secretion and nictitating membrane contraction. The blood flow response to exogenous noradrenaline did, however, not mimic the effects of sympathetic nerve stimulation with regard to vascular escape. Whereas the vascular escape after nerve stimulation was followed by a prolonged vasoconstriction with a gradual decline, the escape after noradrenaline infusions was accompanied by a normalization of blood flow. Local intra-arterial infusions of pancreatic polypeptide (PP)-related peptides caused a slowly developing vasoconstriction with a long duration in the submandibular gland, but no salivary secretion or contraction of the nictitating membrane. The relative molar potencies as vasoconstrictory agents were about PYY: 1, neuropeptide Y (NPY): 5, avian and bovine pancreatic polypeptid 100. The vasoconstrictor effects of PP-related peptides were resistant to α-adrenoceptor blockade and present also in sympathectomized animals, suggesting a direct action on vascular smooth muscle. Combined local infusions of noradrenaline and NPY caused a vascular response in the submandibular salivary gland which was similar to that seen upon sympathetic nerve stimulation. PYY and NPY caused increase in systemic arterial blood pressure upon systemic administration which indicates general vasoconstrictor actions. This effect was accompanied by a transient bradycardia which was due to inhibition of sympathetic tone, since it was absent in animals treated with propranolol. In conclusion, the present findings illustrate the differential sensitivity to α-adrenoceptor antagonists of the submandibular vasoconstriction and salivation as well as smooth muscle contraction of the nictitating membrane induced by sympathetic nerve stimulation. This remaining vasoconstriction may be explained by release of a nonadrenergic, PP-related transmitter such as NPY which may be present together with noradrenaline in the vascular nerves. Release of an additional vasoconstrictory factor may also account for the finding that infusions of noradrenaline do not mimic the vascular effects of sympathetic nerve stimulation in vivo.     

Electrophysiological events during neuroeffector transmission in the spleen of guinea-pigs and rats.

Intracellular recordings were made from smooth muscle cells of arterioles and the capsule of the spleen of guinea-pig and rat, and the responses to periarterial or subcapsular nerve stimulation were recorded. The innervation of the spleen was studied using fluorescence and immunohistochemical techniques. Catecholamine-containing axons were associated with smooth muscle of the splenic capsule, trabeculae, arterioles and amongst cells of the periarteriolar lymphoid sheath. Axons immunoreactive for neuropeptide Y (NPY) and tyrosine hydroxylase were distributed in an identical manner to catecholamine-containing axons, whereas axons immunoreactive for substance P or calcitonin gene-related peptide were present at a very low density in spleens from both species. In segments of arterioles, single transmural stimuli evoked excitatory junction potentials (EJPs) of 1-10 mV amplitude. EJPs facilitated during short trains of stimuli (1-10 Hz) and summated at 10 Hz, often initiating a muscle action potential. EJPs persisted in the presence of prazosin (1 microM) and idazoxan (1 microM), but were abolished by the P2x-purinoceptor antagonist suramin (1 mM). Spontaneous depolarizations were observed in smooth muscle cells of arterioles and capsule. Some events in arterioles were observed in the presence of suramin and so may originate postjunctionally independently of transmitter release. As single transmural stimuli failed to evoke a depolarization in capsular smooth muscle, spontaneous depolarizations in this tissue probably also arise postjunctionally. Short trains of high frequency stimuli (10-35 Hz) evoked biphasic depolarizations of capsular smooth muscle cells. The initial component peaked 2.5 s following the onset of stimulation; the second component peaked 15 s following the onset and decayed exponentially with a time constant of 15 s. By fitting a product of exponentials to the second component, it was possible to define the initial component, which decayed with a time constant of around 1.5 s. Neurally evoked depolarizations of capsular smooth muscle were abolished by 1 microM TTX. Blockade of alpha 1-adrenoceptors with prazosin reduced the initial component of the depolarization, whereas alpha 2-adrenoceptor blockade with idazoxan virtually abolished the second component. In some cells a small, faster depolarization persisted after alpha-adrenoceptor blockade. The slow alpha 2-adrenoceptor-mediated depolarization was identical to that recorded in the rat tail artery and in the guinea-pig mesenteric vein. The data indicate that sympathetic neuroeffector transmission from noradrenergic axons containing NPY to splenic arterial and capsular smooth muscle occur by different mechanisms.     

Release of endothelin-like immunoreactivity in relation to neuropeptide Y and catecholamines during endotoxin shock and asphyxia in the pig

The changes in endothelin-like immunoreactivity in plasma during various provocations in the pig were investigated and related to those of neuropeptide Y, noradrenaline and adrenaline. Release as revealed by overflow was determined in the spleen, kidney and femoral vascular bed (skeletal muscle) simultaneously by collecting local venous and arterial blood samples. Under basal conditions there was no net release of endothelin-like immunoreactivity from any region but a net removal (negative overflow) over the kidney. Endotoxin administration (20 micrograms kg-1 h-1 for 4 h) increased arterial endothelin-like immunoreactivity, neuropeptide Y-like immunoreactivity, noradrenaline and adrenaline seven-, 27-, 100- and 166-fold respectively, as well as splenic and renal vascular resistance. An increased overflow of endothelin-like immunoreactivity, neuropeptide Y-like immunoreactivity and noradrenaline, indicating local release, was observed in the spleen during endotoxin administration. The arterial plasma endothelin-like immunoreactivity during endotoxaemia correlated significantly with the splenic and renal vasoconstriction (r = 0.75 and 0.68 respectively). Chromatographic characterization revealed that the main portions of arterial plasma endothelin-like immunoreactivity collected during endotoxaemia corresponded to synthetic endothelin-1 and big endothelin. A similar uptake (50-90%) and plasma half-life (1-2 min) of exogenous endothelin-1-like immunoreactivity was observed both under control conditions and after endotoxin, suggesting that elevated plasma endothelin-like immunoreactivity after endotoxin was the result not of reduced clearance but rather of enhanced release. Asphyxia for 2 min did not increase arterial endothelin-like immunoreactivity but evoked an increased overflow of endothelin-like immunoreactivity, neuropeptide Y-like immunoreactivity and noradrenaline as well as vasoconstriction in the spleen. Capsaicin induced a release of neuropeptide Y-like immunoreactivity and noradrenaline from both the spleen and the kidney and of adrenaline from the adrenal, but no detectable overflow of endothelin-like immunoreactivity from any of the vascular regions. Renal nerve stimulation, renal artery occlusion for 30 min, haemorrhagic shock, hypotension induced by nitroprusside infusion or serotonin did not cause any detectable increase in arterial plasma levels or local overflow of endothelin-like immunoreactivity. It is concluded that plasma levels of endothelin-like immunoreactivity are increased, suggesting release in the pig in response to endotoxin administration and asphyxia. The possible involvement of endothelin as a mediator of the peripheral vasoconstrictor responses during these situations remains to be further established.     

Sympathetic vascular control of the pig nasal mucosa: (I) increased resistance and capacitance vessel responses upon stimulation with irregular bursts compared to continuous impulses

An in vivo model is described in which pentobarbital anaesthetized pigs were used to study the sympathetic nervous control of the nasal mucosal vascular bed. Changes in blood flow in the sphenopalatine artery (representing nasal blood flow) and in the volume of the nasal cavity (mainly reflecting blood content in venous sinusoids), upon electrical stimulation of the cervical sympathetic trunk, were recorded simultaneously. Single impulses (15V, 5 ms) reduced both the arterial flow and the volume of the nasal mucosa. The effects of nerve stimulation with a continuous train of impulses at 0.59, 2 and 6.9 Hz were compared with those caused by stimulation with the irregular bursting pattern, triggered by recorded human sympathetic vasoconstrictor nerve activity, with the same average frequencies. Both types of stimulation reduced nasal blood flow and volume, but the responses were significantly larger with burst stimulation at 0.59 Hz. The volume reduction was already maximal at 0.59 Hz while the blood flow response increased further higher frequencies. Local intra-arterial pretreatment with the α-adrenoceptor antagonist phenoxybenzamine significantly attenuated the flow and volume responses to single impulses, while clear-cut reductions in blood flow (by 40%) and volume (by 80%) remained, upon stimulation, at 6.9 Hz. Noradrenaline given intra-arterially caused a dose-dependent reduction in nasal blood flow and volume. The noradrenaline effects were blocked by phenoxybenzamine treatment. The results show that the pig nasal mucosa represents a model where both blood flow and volume changes can be studied in parallel in vivo. Furthermore, stimulation with the firing pattern of human vasoconstrictor nerves, i.e. irregular bursts, causes larger vascular responses in the pig nasal mucosa compared to a continuous stimulation. The large residual vascular responses to sympathetic nerve stimulation at high frequency after a-adrenoceptor blockage may be mediated by some other non-adrenergic transmitter substance(s).     

Effects of adrenergic stimulants on the splenic diameter,haemoglobin content and haematocrit in anaesthetized dogs: determination of the adrenoceptor subtype responsible for changes in the splenic diameter

Changes in splenic diameter measured by sonomicrometry in response to various adrenergic stimulants were estimated together with simultaneously measured arterial haemoglobin content (HGB) and haematocrit (HCT) in anaesthetized dogs. Splenic diameter decreased following intravenous injections (i.v.) of adrenaline, noradrenaline and phenylephrine and splenic nerve stimulation associated with increases in arterial HGB and HCT, which were significantly attenuated by prazosin i.v. After prazosin i.v., adrenaline i.v. increased splenic diameter significantly, but noradrenaline i.v. did not. Isoprenaline i.v. increased splenic diameter transiently, followed by a decrease that was abolished by prazosin i.v. During occlusion of splenic arteries and veins, adrenaline i.v. and phenylephrine i.v. did not cause any change in arterial HGB and HCT. Injection to splenic artery (i.a.) of phenylephrine induced a significant decrease in splenic diameter that was attenuated by prazosin i.a. but not by yohimbine i.a. Clonidine i.a. did not change splenic diameter. The present results indicate that splenic contraction, which is mediated through α₁-adrenoceptor activation, causes a significant increase in arterial HGB and HCT.     

Sympathetic vascular control of the pig nasal mucosa: (I). Increased resistance and capacitance vessel responses upon stimulation with irregular bursts compared to continuous impulses

An in vivo model is described in which pentobarbital anaesthetized pigs were used to study the sympathetic nervous control of the nasal mucosal vascular bed. Changes in blood flow in the sphenopalatine artery (representing nasal blood flow) and in the volume of the nasal cavity (mainly reflecting blood content in venous sinusoids), upon electrical stimulation of the cervical sympathetic trunk, were recorded simultaneously. Single impulses (15V, 5 ms) reduced both the arterial flow and the volume of the nasal mucosa. The effects of nerve stimulation with a continuous train of impulses at 0.59, 2 and 6.9 Hz were compared with those caused by stimulation with the irregular bursting pattern, triggered by recorded human sympathetic vasoconstrictor nerve activity, with the same average frequencies. Both types of stimulation reduced nasal blood flow and volume, but the responses were significantly larger with burst stimulation at 0.59 Hz. The volume reduction was already maximal at 0.59 Hz while the blood flow response increased further higher frequencies. Local intra-arterial pretreatment with the alpha-adrenoceptor antagonist phenoxybenzamine significantly attenuated the flow and volume responses to single impulses, while clear-cut reductions in blood flow (by 40%) and volume (by 80%) remained, upon stimulation, at 6.9 Hz. Noradrenaline given intra-arterially caused a dose-dependent reduction in nasal blood flow and volume. The noradrenaline effects were blocked by phenoxybenzamine treatment. The results show that the pig nasal mucosa represents a model where both blood flow and volume changes can be studied in parallel in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Possible involvement of neuropeptide Y in sympathetic vascular control of canine skeletal muscle

Sympathetic nerve stimulation (2 min, 2 and 10 Hz) increased perfusion pressure in the blood perfused canine gracilis muscle in situ after pretreatment with atropine, desipramine and beta-adrenoceptor antagonists. This vasoconstriction was accompanied by clear-cut increases in the overflow of endogenous noradrenaline (NA) at both frequencies and, at 10 Hz but not at 2 Hz, also of neuropeptide Y-like immunoreactivity (NPY-LI). The irreversible alpha-adrenoceptor antagonist phenoxybenzamine enhanced the nerve stimulation induced overflows of NA and NPY-LI five- to eightfold and threefold, respectively. The fractional overflows of NA and NPY-LI per nerve impulse were similar in response to the high-frequency stimulation, indicating equimolar release in relation to the tissue contents of the respective neurotransmitter. The maximal vasoconstrictor response elicited by 10 Hz was reduced by about 50% following a dose of phenoxybenzamine which abolished the effect of exogenous NA and the remaining response was more long-lasting. Local i.a. infusion of NPY evoked long-lasting vasoconstriction in the presence of phenoxybenzamine, while the stable adenosine 5(1)-triphosphate (ATP) analogue alpha-beta-methylene ATP was without vascular effects. Locally infused NPY reduced the nerve stimulation evoked NA overflow by 31% (P less than 0.01) at 1 microM in arterial plasma, suggesting prejunctional inhibition of NA release. In conclusion, NPY-LI is released from the canine gracilis muscle upon sympathetic nerve stimulation at high frequencies. There is nerve stimulation evoked vasoconstriction, which is resistant to alpha-adrenoceptor blockade. This may in part be mediated by NPY released together with NA from the sympathetic vascular nerves.     

Reinnervation of Müller's smooth muscle by atypical sympathetic pathways following neonatal ganglionectomy in the rat: structural and functional investigations of enhanced neuroplasticity

Müller's extraocular smooth muscle is reinnervated by sympathetic nerves following denervation by ipsilateral superior cervical ganglionectomy in neonates but not in older animals. Experiments were performed to determine: (1) the source and extent of reinnervation, (2) the role of impulse activity in sympathetic outgrowth and (3) the effects of reinnervation on smooth muscle maturation. Müller's muscles were evaluated structurally (muscle volume, catecholamine histochemistry, retrograde labeling of sympathetic neurons) and functionally (contractile responses to electrical stimulation of postganglionic innervation and adrenoceptor agonist) in control preparations and in muscles following neonatal ipsilateral superior ganglionectomy, ipsilateral decentralization, ipsilateral superior ganglionectomy combined with contralateral decentralization of chemical (guanethidine) sympathectomy. Fluorescent tracer injections of muscles in adult control rats labeled cells in the ipsilateral superior (98%) and middle cervical ganglia. Acute ipsilateral superior ganglionectomy produced complete degeneration of sympathetic innervation of Müller's muscle in neonatal and adult rats. In preparations denervated neonatally and maintained chronically, muscles were reinnervated by neurons in both the contralateral superior and ipsilateral middle cervical ganglia. The total number of neurons reinnervating the muscle was one half that of controls. Sectional density of innervation was 45% of control. Electrical stimulation of postganglionic axons in the contralateral pathway produced muscle contractions with a prolonged time course. Reinnervation alleviated, in part, deficits in muscle volume and contraction which occurred following sustained denervation by chemical sympathectomy. Decentralization decreased ipsilateral muscle volume but did not affect numbers of neurons projecting to or nerve density within the muscle. Stimulation frequencies required to produce a 50% maximum contraction were reduced in these preparations. Decentralization of the contralateral ganglion did not impede sprouting into the denervated muscle, as nerve density and number of labeled cells were comparable to muscles reinnervated by contralateral ganglia with intact preganglionic innervation. However, maximum contraction to electrical stimulation was reduced. Comparisons with ipsilaterally decentralized muscles revealed that increased stimulation frequencies were required for 50% maximum contraction.(ABSTRACT TRUNCATED AT 400 WORDS)     

A scanning and transmission electron microscopic study of contractile trabecules in the rat spleen

The fine structures of contractile trabecules in the splenic red pulp of the rat were examined by electron microscopy to elucidate their participation in the active contraction of the spleen. Numerous fine thready trabecules were developed in the red pulp. They were enveloped with a cytoplasmic layer of reticular cells and consisted of elongated smooth muscle cells, fascicles of collagenous fibrils and elastic fibers. Their fibrous components in the capsular ends extended in a triangular form of fanribs into the fibrous tunica of the capsule. Smooth muscle cell-like interstitial cells (SIC) were situated in the interfibrous spaces. Flattened SICs were affixed with cytoplasmic processes to the elastic lamina. The trabeculocapsular junctions were represented on the elastic lamina by grouped or isolated circular patches with concentrically arranged triangular processes and were also observed on the capsular serosa by plaques with scarce microvilli of serosal cells. Smooth muscle cells of the fine trabecules were equipped on the cell surface with anchoring structures to extracellular fibrous elements as previously described by Gabella (1981). Close associations were also seen between the smooth muscle cells and elastic fibers which were terminated to the fascicles of collagenous fibers. Cell-to-cell connections were expressed by fibrous connections between spiny processes and a small number of puntate intermediate junctions and nexuses. Unmyelinated nerve fibers with adrenergic terminals were seen in the intercellular spaces. We propose that for the rat spleen, the fine trabecules in the red pulp are muscular contractiles which are responsible for the active contraction due to sympathetic stimuli and the administration of alpha 1-adrenoceptor agonists, while the elastic lamina in the capsule plays a role in the comprehensive contraction of the subcapsular vascular bed.     

Transmission from vasoconstrictor and vasodilator nerves to single smooth muscle cells of the guinea-pig uterine artery

1. Previous studies have shown that perivascular nerve stimulation of the uterine artery of the guinea-pig evokes an adrenergic constrictor response and a dilator response with two components. The first of these, only present during pregnancy, is cholinergic. The second is non-cholinergic and is present at all times. Intracellular recording from single smooth muscle cells in isolated arterial segments has now been used to investigate the transmission processes associated with these responses.2. The mean resting membrane potential of the muscle cells was 60.7 mV in arteries from both virgin animals (range 50-68 mV) and from animals in late pregnancy (range 48-76 mV).3. Low frequency perivascular stimulation evoked excitatory junction potentials (EJPs) which reached a maximum amplitude of about 5 mV, lasted about 900-1000 msec, and showed facilitation at frequencies of stimulation of 0.1 Hz or above and summation at frequencies of stimulation of 1.2 Hz or above.4. These EJPs were abolished by exposure of the tissue to bretylium (2 x 10(-6) g/ml.). It is therefore concluded that the EJPs were due to transmission from adrenergic nerves.5. Perivascular stimulation at frequencies above 10 Hz evoked a depolarizing response which was often surmounted by a small (5 mV) local spike potential. Such depolarizing responses were associated only with localized contractions of the arterial muscle.6. In the presence of low extracellular K(+) concentrations, perivascular stimulation at frequencies above 10 Hz gave rise to a depolarizing response topped by an action potential of up to 50 mV amplitude, and more generalized contraction of the tissue than was seen in normal K(+) solution.7. After blockade of the adrenergic vasoconstrictor fibres, no response to perivascular stimulation was observed normally. However, following moderate depolarization of the membrane with noradrenaline, stimulation evoked a hyperpolarization of up to 6 mV in amplitude.8. This response showed no discrete junction potentials, had a latency of up to 2000 msec and was only observed with stimulation at frequencies of 2 Hz or greater. The response was obtained in both pregnant and non-pregnant animals, and was unaffected by hyoscine, but was abolished by cinchocaine.9. No changes in membrane potential attributable to transmission from cholinergic dilator nerves could be revealed in arteries from pregnant animals. Furthermore, high concentrations of acetylcholine had no polarizing effect on the muscle cells. It is suggested that the cholinergic dilator nerves may not act via changes in membrane potential.     

Vasodilatation and modulation of vasoconstriction in canine subcutaneous adipose tissue caused by activation of beta-adrenoceptors.

The present experiments were undertaken to study the balance between vascular alpha- and beta-adrenoceptors in canine subcutaneous adipose tissue during sympathetic nerve stimulation and noradrenaline injections. Propranolol potentiated and prolonged the vasoconstrictor response to close i.a. injections of noradrenaline. The vasoconstriction induced by brief nerve stimulation (0.5 to 8 Hz) was, however, unaltered by the beta-adrenoceptor blockade. During prolonged nerve stimulation the vasoconstrictor response was well maintained at 1.5 Hz but at 4 Hz there was a gradual escape. The escape phenomenon at 4 Hz was diminished by propranolol. The beta1-selective antagonist practolol, like propranolol, potentiated and prolonged the vasoconstriction induced by noradrenaline injections and reduced the vasoconstrictor escape during prolonged nerve stimulation at 4 Hz. Furthermore, the vasodilatation induced by noradrenaline injection or nerve stimulation during alpha-adrenoceptor blockade was diminished by practolol. Practolol also blocked the lipolytic response to noradrenaline and nerve stimulation. The beta2-selective antagonist H35/25 blocked the effects of the beta2-selective agonist salbutamol but failed to alter noradrenaline as well as nerve stimulation induced vascular and lipolytic beta-adrenoceptor responses. The present results provide further support for the hypothesis that vascular beta-adrenoceptors in adipose tissue are humoral (noninnervated), preferentially activated by circulating noradrenaline. Moreover, both vascular and lipolytic beta-adrenoceptors activated by noradrenaline in adipose tissue are best classified as beta1-adrenoceptors.     

Transmitter characteristics of cutaneous,renal and skeletal muscle small arteries in the rat

Aim: We studied transmitter characteristics of proximal and distal arteries supplying skin (saphenous artery and its medial tarsal branch), kidneys (terminal branches of renal artery and interlobar arteries) and skeletal muscle (proximal and distal sections of external sural artery). Methods: Artery segments were mounted in an isometric myograph and intramural nerves were activated by electrical field stimulation. Adrenergic and purinergic components of the neurogenic response were blocked using phenoxybenzamine and α,β‐methylene adenosine triphosphate (mATP), respectively. Results: Arteries from skin or kidney developed rapid and prominent neurogenic contractile responses, with half‐maximal amplitude reached within 5–15 s; responses in proximal vessels were greater than in distal vessels. Arteries from skeletal muscle responded to sympathetic stimulation with a moderate contraction developing over 1 min or more, the response of distal segments was greater than that of proximal segments. In skeletal muscle vessels the sympathetically evoked contraction was completely blocked by phenoxybenzamine, whereas in skin and renal vessels it was the combined effect of noradrenaline and adenosine triphosphate (ATP). Given alone, mATP did not change the magnitude of the response to nerve stimulation, but increased its latency and also potentiated the response to exogenous noradrenaline. In all vascular beds, distal vessels were more sensitive to noradrenaline and mATP. Conclusion: It thus appears that the noradrenaline/ATP ratio of the sympathetic vasoconstrictor response differs between vascular beds in a way that is consistent with known differences in the selective regulation of regional vascular resistance by the sympathetic nervous system.     

Transmitter characteristics of cutaneous,renal and skeletal muscle small arteries in the rat

AIM: We studied transmitter characteristics of proximal and distal arteries supplying skin (saphenous artery and its medial tarsal branch), kidneys (terminal branches of renal artery and interlobar arteries) and skeletal muscle (proximal and distal sections of external sural artery). METHODS: Artery segments were mounted in an isometric myograph and intramural nerves were activated by electrical field stimulation. Adrenergic and purinergic components of the neurogenic response were blocked using phenoxybenzamine and alpha,beta-methylene adenosine triphosphate (mATP), respectively. RESULTS: Arteries from skin or kidney developed rapid and prominent neurogenic contractile responses, with half-maximal amplitude reached within 5-15 s; responses in proximal vessels were greater than in distal vessels. Arteries from skeletal muscle responded to sympathetic stimulation with a moderate contraction developing over 1 min or more, the response of distal segments was greater than that of proximal segments. In skeletal muscle vessels the sympathetically evoked contraction was completely blocked by phenoxybenzamine, whereas in skin and renal vessels it was the combined effect of noradrenaline and adenosine triphosphate (ATP). Given alone, mATP did not change the magnitude of the response to nerve stimulation, but increased its latency and also potentiated the response to exogenous noradrenaline. In all vascular beds, distal vessels were more sensitive to noradrenaline and mATP. CONCLUSION: It thus appears that the noradrenaline/ATP ratio of the sympathetic vasoconstrictor response differs between vascular beds in a way that is consistent with known differences in the selective regulation of regional vascular resistance by the sympathetic nervous system.     

Cardiovascular and sympathoadrenal responses to mental stress: a study of sensory intake and rejection reactions

Cardiovascular, sympathoadrenal and subjective responses to mental stress induced by two mental challenges eliciting sensory intake (word identification test = WIT) and sensory rejection (colour word conflict test = CWT) reactions were studied in 10 healthy males. Pressor responses to these stressors have been proposed to differ haemodynamically. Sympathoadrenal activity was assessed by arterial and femoral venous plasma catecholamine determinations and direct recordings of muscle sympathetic activity in the right peroneal nerve (MSA). Basal measurements differed little from those made during an active relaxation procedure, with the exception of MSA, which decreased. Both stress tasks elicited increases in heart rate, cardiac output, calf blood flow and brachial and pulmonary arterial blood pressures. WIT and CWT elicited qualitatively similar responses, but the amplitudes of the circulatory responses were lower with WIT, which also was rated as a weaker stressor. MSA increased during CWT, while marginal increases were seen during WIT. Arterial adrenaline showed a transient increase by 0.14 nmol l-1 during WIT. During CWT arterial adrenaline increased significantly by 50%. Increases in arterial adrenaline and subjective stress ratings were related to increases in cardiac output and reductions of systemic vascular resistance. Arterial and femoral venous noradrenaline increased during CWT, while changes during WIT were small. MSA and noradrenaline responses did not correlate to local vascular responses in the calf. Differences in the responses to mental challenges evoking sensory intake or rejection seem to be of a quantitative rather than a qualitative character.     

Glucagon inhibition of hepatic arterial responses to hepatic nerve stimulation

The hepatic arterial vascular bed of the chloaralose-urethan-anesthetized dog was perfused with blood from a cannulated femoral artery. Hepatic arterial blood flow and perfusion pressure were measured. The hepatic periarterial postganglionic sympathetic nerves were stimulated supramaximally at 0.1, 0.5, 1, 2, 5, 10, and 20 Hz; this caused frequency-dependent rises in the calculated hepatic arterial vascular resistance at all frequencies above the threshold of 0.1 or 0.5 Hz. Glucagon was infused intra-arterially in dosese from 0.25 to 10 microgram/min; glucagon antagonized both the vasoconstrictor effects of hepatic nerve stimulation and of intra-arterial injections of norepinephrine. The degree of antagonism of these responses was significantly correlated with the calculated hepatic arterial glucagon concentration. It is possible that glucagon released physiologically in stress and hypoglycemia may protect the hepatic arterial vasculature from the effects of increased sympathetic discharge.     

Vascular adrenergic responses in morphine-dependent rats

The circulatory effects of morphine abstinence have recently been found to involve decreased renal sympathetic nerve activity and increased mean arterial pressure, induced by vasoconstriction. A direct influence of morphine withdrawal on the peripheral vasculature could possibly contribute to the increased resistance. Therefore, contractile responses to transmural nerve stimulation and to applied noradrenaline of peripheral arteries from morphine-dependent and untreated rats were examined in vitro under paired conditions. No increase in contractile response was observed after chronic morphine treatment, either on nerve stimulation or on applied noradrenaline. Instead the smooth muscle sensitivity to adrenergic stimulation was reduced. Consequently, the present study does not support a peripheral adrenergic origin of the vasoconstriction during naloxone-precipitated morphine abstinence.