Prejunctional beta 2-adrenoreceptor blockade reduces nerve stimulation evoked release of endogenous noradrenaline in skeletal muscle in situ

Prejunctional beta-adrenoceptor-mediated modulation of endogenous noradrenaline (NA) overflow elicited by sympathetic nerve stimulation was studied in blood-perfused canine gracilis muscle in situ. An attempt was made to subclassify these beta-adrenoceptors by comparing the effects of beta 1-selective (metoprolol) and non-selective (propranolol) beta-adrenoceptor blockade. Animals were pre-treated with desipramine and phenoxybenzamine in order to counteract possible influences of neuronal uptake and stimulation-evoked changes in vascular resistance on the diffusion of NA into the blood stream. Metoprolol did not decrease stimulation-evoked NA overflow, as compared with control experiments (-10 and -8%, respectively). However, propranolol reduced stimulation-evoked NA overflow by 30% in metoprolol pre-treated animals (P less than 0.05 vs. control experiments). Both antagonists elevated basal perfusion pressure, suggesting that vascular post-junctional beta 1- as well as beta 2-adrenoceptors are present. Propranolol increased stimulation-evoked vasoconstriction in metoprolol pre-treated animals, indicating that neuronally released NA may activate postjunctional beta 2-adrenoceptors under these experimental conditions. In conclusion, our findings suggest that NA release can be enhanced by activation of prejunctional beta 2-adrenoceptors in vivo.     

Influence of angiotensin II, α- and β-adrenoceptors on peripheral noradrenergic neurotransmission in canine gracilis muscle in vivo

Interactions between angiotensin II and adrenoceptor-mediated effects on peripheral sympathetic neurotransmission were investigated in constant flow blood-perfused canine gracilis muscle in situ, without and with pretreatment by non-competitive α- adrenoceptor blockade. Angiotensin converting enzyme (ACE)-inhibition by benazeprilat increased nerve stimulation (2 Hz, 4 min)-evoked noradrenaline (NA) overflow (+21 ± 5 yo) with α- adrenoceptors intact, but reduced NA overflow (– 18 ± 6%) when α-adrenoceptors were blocked. Vasoconstrictor responses were slightly reduced by benazeprilat. Subsequent infusion of angiotensin II (Ang 11, 20 and 500 ng kg_-1 min_-1 i.v., raising arterial concentrations from 0.6 ± 0.2 PM to 1390 ± 240 and 25 110 ± 3980 PM, respectively) failed to increase NA overflow or to enhance stimulation-evoked vasoconstriction. Adrenaline (0.4 nmol kg_-1 min_-1 i.v.) did not change evoked NA overflow before or after benazeprilat, either with or without α-adrenoceptor blockade, despite high concentrations (± 10 nM) in arterial plasma. Following benazeprilat, propranolol reduced NA overflow (–24 ± 3 yo) only if the α-adrenoceptors were blocked. In conclusion, benazeprilat reduced evoked NA overflow in the presence of α- adrenoceptor blockade to a similar degree as previously shown in the presence of neuronal uptake inhibition in this model. However, contrasting to our previous findings, benazeprilat enhanced NA overflow and reduced the post-junctional response to nerve stimulation in the absence of α-adrenoceptor blockade. This could be related to bradykinin accumulation during ACE-inhibition, in addition to the reduction of Ang II generation. Our data are not compatible with facilitation of NA release by circulating Ang II even at pharmacological dose levels. Although activation of prejunctional β-adrenoceptors may facilitate evoked NA overflow in this model, circulating adrenaline is ineffective under physiological conditions even after α-adrenoceptor blockade. Also, β-adrenoceptor-mediated prejunctional effects do not seem to involve Ang II in canine skeletal muscle in vivo.     

β2-Adrenoceptors Facilitating Noradrenaline Secretion from Human Vasoconstrictor Nerves

Isolated superfused biopsy specimens of human peripheral arteries and veins, preincubated with ³H-(-)-noradrenaline (NA) to label the neural stores of NA, were used to study the β-adrenoceptors previously found to increase the secretion of ³H-NA evoked by electrical field stimulation of the adrenergic nerves of this tissue. The increase in nerve stimulation induced secretion of ³H-NA caused by 0.04μM isoprenaline was prevented by 1 μM propranolol. This &bT-blocking drug by itself slightly but significantly depressed the secretion of ³H-NA caused by nerve stimulation in the absence of isoprenaline. While the secretion of ³H-NA was not affected by two known β₁-agonists, it was dose-dependently and reversibly increased by two different β₂-agonists. The effect of isoprenaline on ³H-NA secretion was not altered by a selective β-antagonist, but strongly reduced or abolished by a β₂-blocking drug. The results indicate that the β-adrenoceptors involved in the control of NA secretion from the vasoconstrictor nerves of human omental blood vessels are only to a minimal extent stimulated by NA secreted from the nerves, and therefore do probably not mainly serve to mediate local positive feedback control of transmitter secretion; the receptors appear to be β₂ in nature.     

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

The present experiments were undertaken to study the balance between vascular α- and β-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 β-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 β₁-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 α-adrenoceptor blockade was diminished by practolol. Practolol also blocked the lipolytic response to noradrenaiine and nerve stimulation. The β₂-selective antagonist H35/25 blocked the effects of the β₂-selective agonist salbutamol but failed to alter noradrenaline as well as nerve stimulation induced vascular and lipolytic β-adrenoceptor responses. The present results provide further support for the hypothesis that vascular β-adrenoceptors in adipose tissue are humoral (noninnervated), preferentially activated by circulating noradrenaline. Moreover, both vascular and lipolytic β-adrenoceptors activated by noradrenaline in adipose tissue are best classified as β₁-adrenoceptors.     

β1-and β2-adrenoceptor-mediated secretion of amylase from incubated rat parotid gland

The present in vitro investigation was undertaken in an attempt to obtain further information on β-adrenoceptor specificity and action in the rat parotid gland, with regard to amylase secretion. The β₁-selective agonist prenalterol was roughly 800 times more potent than the β₂-agonist terbutaline, and about 5 times more effective than noradrenaline in evoking amylase release. Propranolol was the most effective inhibitor of amylase release in all experiments. The β₁-selective antagonist metoprolol and H104/08 were also effective blockers of maximal noradrenaline-and prenalterol-induced release. The inhibition curves displayed biphasic shapes when amylase secretion was induced by noradrenaline, but not when prenalterol was the secretagogue. The β₂-antagonist H35/25 was without effect on maximal noradrenaline-and prenalterol-stimulated secretion. The amylase release evoked by submaximal concentration of terbutaline was inhibited by the two antagonists H35/25 and IPS 339. In another series of experiments propranolol and metoprolol clearly shifted the noradrenaline concentration-response curve to the right, whereas H35/25 was without effect. The results further demonstrate the major importance of the β₁-adrenoceptor (noradrenaline-activated) in eliciting amylase release from the rat parotid gland. However, it is also suggested that the β₂-adrenoceptors (terbutaline-activated) may to some extent serve the same function.     

Blockade of central β-adrenoceptors attenuates tremor induced by 5-hydroxytryptamine (5-HT)-receptor activation in rats

The effect of β-adrenoceptor antagonists, varying in lipophilicity and receptor selectivity, were studied on tremor elicited by l -5-hydroxytryptophan (L-5-HTP) in rats pretreated with a peripherally acting decarboxylase inhibitor and a monoamine oxidase inhibitor, or by the directly acting 5-HT agonist s-methoxy-N,N-dimethyltryptamine (5-MeODMT). Plasma levels of the β-adrenoceptor antagonists were determined simultaneously. The non-selective lipophilic adrenoceptor antagonist propranolol was found to dose-dependently reduce tremor intensity, whereas the non-selective hydrophilic adrenoceptor antagonist sotalol had no effect, indicating a central site of action. Furthermore, β₁-selective blockade with the adrenoceptor antagonist metoprolol had no effect on tremor intensity, whereas the β₂-selective antagonist ICI 118,551 dose-dependently suppressed tremor intensity, suggesting that the β-adrenoceptor subtype involved is of the β₂-type. These results suggest that blockade of centrally located β₂-adrenoceptors are able to attenuate the tremor response following 5-hydroxytryptamine receptor activation.     

Modulation of oxotremorine-induced tremor by central β-adrenoceptors

The muscarinic agonist oxotremorine was used to induce tremor in rats pretreated with methylatropine. An objective assessment of tremor intensity was accomplished by means of an accelerometer-based recording system. The non-selective, lipophilic β-adrenoceptor antagonist propranolol dose-dependently suppressed tremor intensity, whereas the r -isomer of propranolol was without effect, verifying β-adrenoceptor involvement. Since the hydrophilic, non-selective β-antagonist nadolol was ineffective, the effect appears to be located inside the blood-brain barrier. The β₂-selective antagonist ICI 118, 551 dose-dependently reduced tremor intensity, whereas selective blockade of β₁-adrenoceptors with metoprolol had no effect, indicating the participation of a β₂-adrenoceptor. On the other hand, the lipophilic β₂-agonist clenbuterol dose-dependently enhanced tremor induced by oxotremorine. Determination of circulating plasma catecholamine concentrations revealed that the effect of β-antagonists on tremor was not secondary to an effect on the oxotremorine-induced rise in catecholamine levels. Thus, the results suggest that β₂-adrenocpetors located inside the blood-brain barrier are able to modulate oxotremorine-induced tremor in rats.     

Facilitatory effect of adrenocorticotropic hormone and related peptides on ca2+-dependent noradrenaline release from sympathetic nerves

Strips of rabbit pulmonary artery and aorta were incubated with [ ³H]noradrenaline and subsequently superfused. Tritium overflow from strips superfused with physiological salt solution was stimulated either electrically (usually at a frequency of 2 Hz) or by tyramine 1 μmol/l and overflow from strips superfused with Ca²⁺-free solution containing K⁺ 54.7mmol/l was stimulated by introduction of Ca²⁺ 1.6mmol/l. In most of the experiments (stimulation by electrical impulses or CaCl²) neuronal and extraneuronal uptake and β-adrenoceptors were blocked by cocaine, corticosterone and propranolol, respectively. The electrically evoked overflow of ³H-labelled substances from pulmonary artery and aorta was increased by adrenocorticotropic hormone_1–24. In the pulmonary artery, the adrenocorticotropic hormone_1–24—induced increase in impulse—evoked overflow (and contraction) was the more pronounced, the lower the frequency of stimulation (6, 2 and 0.66 Hz: 360 impulses). The electrically evoked overflow of ³H-labelled substances was also increased by α-melanocyte-stimulating hormone and porcine adrenocorticotropic hormone, but was not affected by adrenocorticotropic hormone_4–10. Adrenocorticotropic hormone_1–24 also facilitated the Ca²⁺-evoked overflow of ³H-labelled substances promoted by high K⁺, but it did not affect the Ca²⁺-independent tyramine-evoked overflow. Adrenocorticotropic hormone_1–24 did not alter the percentages of [ ³H]noradrenaline and ³H-labelled metabolites contained in electrically or tyramine-evoked overflow of ³H-labelled substances.In conclusion, adrenocorticotropic hormone and fragments of adrenocorticotropic hormone cause an increase in stimulation-evoked, Ca²⁺-dependent noradrenaline release from postganglionic sympathetic nerve fibres, probably by activating presynaptic receptors for adrenocorticotropic hormone.     

β2-adrenergic control of plasma volume in hemorrhage

Hemorrhage is associated with absorption of extravascular fluid from skeletal muscle to blood in order to compensate for the loss of intravascular volume. Our previous studies have shown that this fluid gain is mainly linked to β-adrenergic microvascular adjustments leading to decrease in capillary hydrostatic pressure and to precapillary ‘sphincter’ mediated increase in the capillary surface area available for fluid exchange. In the present study the importance of β-adrenergic control of plasma volume in bleeding was confirmed by measurement of changes in plasma volume after graded hemorrhage in animals with intact and blocked vascular β₂-adrenoceptors (i. v. administration of the ‘selective’β₂-blocking agent ICI 118, 551). With intact β₂-adrenoceptors plasma volume was gradually restored after bleeding so that about 50% of the shed plasma volume (about 35% of the shed blood volume) had been compensated for at two hours after exsanguination of 20% as well as 40% of the blood volume. The corresponding figures in animals with blocked β₂-adrenoceptors were only 14% of the shed plasma volume and 8% of the shed blood volume at both degrees of hemorrhage.     

Influences on central hemodynamics in hemorrhage of β2-adrenergic vascular control mechanisms

Central hemodynamic responses evoked by standardized hemorrhage (exsanguination of 20 ml×kg bwt^-1) were followed during 2 h in cats with intact and blocked vascular β₂-adrenoceptors using the ‘selective’β₂-blocker, ICI 118, 551. In the first 10 min after bleeding blood pressure and cardiac output (CO) decreased and total peripheral resistance (TPR) increased by the same amount in the ‘intact’ and β₂-blocked animals. Whereas blood pressure later on reached approximately the same hypotension level in both groups, other hemodynamic variables were distinctly different. In the ‘intact’ animals there was a gradual, partial recovery of stroke volume (SV) and CO in the face of a restoration to control of TPR. In the β₂-blocked animals TPR continued to increase in the face of a maintained low CO and declining SV. The lower SV in the latter group was ascribed to abolition of β₂-adrenergic restoration of plasma volume via absorption of tissue fluid into the circulation. The gradual decline of TPR in the ‘intact’ animals was attributed to β₂-adrenergic dilator interaction with constrictor influences on the resistance vessels. It is concluded that β-adrenergic vascular control mechanisms help to improve nutritional tissue blood flow during hemorrhage by increasing plasma volume, and hence venous return and CO, and by decreasing TPR. These reflex, β₂-adrenergic circulatory events are similar to those aimed at in current shock therapy by transfusion and vasodilator treatment.     

The effect of β-receptor blockade on adrenaline-induced changes in redox and energy state in m. vastus lateralis and m. soleus of the rat in vivo

The metabolic changes in blood, red (m. soleus) and white (m. vastus lateralis) skeletal muscle fibres were investigated after short-term (3 min) infusion of adrenaline with or without prior treatment with propranolol or metoprolol. The adrenaline-induced increase in plasma lactate levels was totally prevented by prior treatment with metoprolol or propranolol, whilst the β-blockers had no effect on blood glucose levels. Similar effects on lactate levels were found in the m. soleus, while metoprolol was less effective than propranolol in m. vastus lateralis. Adrenaline decreased the level of muscle creatinine phosphate and ADP, causing the equilibrium of the creatinine kinase reaction to change in the direction of ATP synthesis, although the level of ATP usually decreased. This effect was more pronounced in m. vastus lateralis compared with m. soleus. The [ATP]/[ADP] [Pi]-ratio tended to increase during infusion of adrenaline. This effect was counteracted by metoprolol but not by propranolol. The effects on the “phosphate potential” ([ATP]/[ADP] [Pi]) and the equilibrium within the creatine kinase were more pronounced in m. vastus lateralis than in m. soleus. The results demonstrate the possible role of receptors other than β-receptors, i.e. α-receptors, in mediating changes in plasma glucose levels, while plasma lactate levels are regulated by the β-adrenergic system. The role of β-receptors in mediating changes in muscle lactate levels may differ in m. soleus and m. vastus lateralis, with a relative predominance of β₂-_-receptors in m. vastus lateralis. Quantitative and qualitative differences in the adrenergic control of the energy state in the two types of muscle fibre were obvious, although it was not possible to distinguish clearly between the relative importance of α₁β₁ and β_2-receptors.     

Fluid and protein secretion from ferret submandibular and parotid glands in response to sympathetic nerve stimulation or administration of sympathomimetics.

Electrical stimulation of the sympathetic innervation evoked secretion of submandibular and parotid saliva. By changing the mode of stimulation from a continuous to an intermittent one the fluid response increased and glandular blood flow improved. The volumes from the submandibular glands were larger than those from the parotid glands and further, the protein concentration of submandibular saliva was higher than that of parotid saliva. Adrenaline, isoprenaline and phenylephrine evoked larger fluid responses from submandibular than from parotid glands. However, the fluid response was small compared to the parasympathetic one. Substance P-evoked saliva was used as carrier for protein released by sympathetic nerve stimulation or administration of adrenaline and isoprenaline. In vitro tissues of submandibular and parotid glands responded to adrenaline with a dose-dependent release of protein. Taken together, the analytical pharmacology performed in vivo and in vitro, and including the antagonists phentolamine, dihydroergotamine, propranolol and metoprolol, showed that in submandibular glands, α(α₁)adrenoceptors were predominantly involved in fluid secretion and β(β₁)-adrenoceptors predominantly involved in protein secretion. In parotid glands, fluid secretion seemed solely to depend on α(α₁)-adrenoceptors, while β(β₁)-adrenoceptors seemed almost solely involved in protein secretion.     

Autoradiographic location of β-adrenoceptor subtypes in cat colon smooth muscle

In order to localize β-adrenoceptors ¹²⁵I-(—)pindolol (IPIN) was used in binding to sections from cat colon. The binding characteristics for IPIN to β-adrenoceptors on colon sections were estimated by demonstrating reversible binding in the presence of isoprenaline and by steroselective binding to the isomers of propranolol. The binding of IPIN to both β₁-and β₂-adrenoceptors was shown by biphasic displacement curves in the presence of the selective β-adrenoceptor compounds betaxolol, ICI 118.551 and procaterol. The colon sections were found to contain proportions of β₁-adrenoceptors (30–50%) and β₂-adrenoceptors (50–70%). In the autoradiographic studies, 100% of the developed grains after exposure of IPIN to the photographic emulsion were displaced by 50 μm of isoprenaline. By microscopic counting at autoradiographic grains, 30–40% of the grains were found in the circular smooth muscle, while 60–70% of the grains were found in the longitudinal smooth muscle. A concentration of 2 nm ICI 118.551 completely displaced all grains in the circular smooth muscle and partly displaced those found in the longitudinal smooth muscle. A high concentration of ICI 118.551 (1 μm ) displaced all grains above background from the smooth muscle. It is concluded that the circular smooth muscle only contains β₂-adrenoceptors, while longitudinal smooth muscle may contain a proportion of β₁-adrenoceptors. Whether such a location of β-adrenoceptors can be related to the β₁-adrenoceptor-mediated inhibition of colon motility can not be clarified from these studies. However, it seems that β₁-adrenoceptors are located to the longitudinal smooth muscle instead of to the myenteric plexus of the colon.     

Acute blockade of β1-receptors in the asphyxiated sheep fetus

Acute blockade of β₁-receptors in the asphyxiated sheep fetus. Acta Physiol Scand 130 , 381–385. Received 5 November 1986, accepted 9 February 1987. ISSN 0001–6772. Department of Paediatrics, Landspitalinn, University Hospital, Reykjavik, Iceland and Department of Physiology and Department of Paediatrics I, University of Goteborg, Sweden. The effects of acute β₁-blockade on fetal cardiovascular reactions during asphyxia were evaluated in 11 exteriorized sheep fetuses. Gestational age was 110–142 days. Asphyxia was induced either by ventilating the mother with low oxygen gas mixture or by mechanical reduction of placental blood flow. During asphyxia all fetuses reacted to metoprolol injection with a decrease in heart rate, myocardial contractility, cardiac output and arterial blood pressure. Five experiments resulted in irreversible fetal cardiovascular collapse. Isoprenaline was given to the fetuses during hypoxia to test the ability to further increase heart rate and activate myocardial β-adrenoceptors. In those experiments with fetal cardiovascular demise after metoprolol, the isoprenaline injection did not result in a significant tachycardia. The surviving fetuses could increase their heart rate as a sign of a capacity to further increase the sympatho-adrenergic drive.     

Decrease in survival time in β2-adrenoceptor blocked cats exposed to bleeding

Our previous investigations have indicated that β₂-adrenergic regulatory mechanisms contribute to important compensatory hemodynamic adjustments in hemorrhage. In the present study an attempt was made to examine, by comparative observations after standardized fatal hemorrhage on cats with intact and ‘selectively’ blocked β₂-adrenoceptors (ICI 118,551), whether such compensatory effects are crucial for survival. On the average, the survival time after bleeding was 686 min in cats with intact and 427 min in cats with blocked β₂-adrenoceptors (p < 0.05), the difference thus approaching 4.5 h. It is suggested that the reduced survival time after β₂-blockade, at least partly, can be ascribed to interference with the circulatory β₂-adrenergic control in hemorrhage aimed at improving tissue perfusion.     

Time-dependent effects of ischaemia on neuropeptide Y mechanisms in pig renal vascular control in vivo

We have investigated the effects of ischaemia on neuropeptide Y (NPY) mechanisms involved in sympathetic vascular control of the pig kidney in vivo. Reperfusion after 2 h of renal ischaemia was associated with local overflow of noradrenaline (NA) but not of NPY-like immunoreactivity (-LI). Renal sympathetic nerve stimulation 10 min into reperfusion evoked markedly reduced vasoconstrictor effects and significantly less overflow of NA (reduced by 70% from the pre-ischaemic conditions), whereas NPY-LI overflow was unaltered. Renal vasoconstrictor responses to exogenous peptide YY (PYY), phenylephrine and angiotensin II were strongly attenuated after this ischaemic period, while vasoconstriction to α,β-methylene ATP was maintained to a larger extent. The renal vascular responses and NA overflow had become partially normalized within a 2 h recovery period. In contrast, the renal vasoconstrictor response and the overflow of NPY-LI upon sympathetic nerve stimulation were enhanced after 15 min of renal ischaemia. In parallel, the PYY-evoked renal vasoconstriction was selectively and markedly prolonged after the 15 min of ischaemia. In the presence of the NPY Y₁ receptor antagonist BIBP 3226, the augmented vascular response to nerve stimulation was significantly attenuated. We conclude that reperfusion after 2 h of renal ischaemia is associated with local overflow of NA, whereas the sympathetic nerve-evoked release of NA and the reactivity of the renal vasculature to vasoconstrictor stimuli are reversibly reduced. Furthermore, possibly due to an impaired local degradation, the role of neurogenically released NPY in renal sympathetic vasoconstriction is enhanced after short-term (15 min) ischaemia compared with control conditions.     

Release and vasoconstrictor effects of neuropeptide Y in relation to non-adrenergic sympathetic control of renal blood flow in the pig

The possible involvement of neuropeptide Y (NPY) in sympathetic control of renal blood flow was investigated in the pig in vivo. Exogenous NPY caused renal vasoconstriction with a threshold effect at an arterial plasma concentration of 164 pmol 6(-1). Stimulation of the renal nerves (0.59, 2 and 10 Hz) in control animals evoked rapid and frequency-dependent reduction in renal blood flow and overflow of NPY-like immunoreactivity (NPY-LI) and noradrenaline (NA) from the kidney, suggesting co-release from sympathetic nerves. Following the administration of the alpha- and beta-adrenoceptor antagonists phenoxybenzamine and propranolol, the vasoconstrictor response to exogenous NA was reduced by 98%, whereas that of NPY was unaltered. The response to nerve stimulation with 0.59 Hz was abolished, whereas relatively slowly developing reductions in renal blood flow by 7 and 28% were obtained upon stimulation with 2 and 10 Hz respectively. The nerve stimulation-evoked overflow of NA at 0.59 and 2 Hz, but not at 10 Hz and not that of NPY-LI, was enhanced after adrenoceptor blockade. Twenty-four hours after reserpine treatment (1 mg kg-1 i.v.) the contents of NPY-LI and NA in the renal cortex were reduced by 80 and 98% respectively. Sectioning of the renal nerves largely prevented the reserpine-induced depletion of NPY-LI, but not that of NA. Nerve stimulation of the denervated kidney with 2 and 10 Hz 24 h after reserpine treatment evoked slowly developing and long-lasting reductions in renal blood flow by 6 and 52% respectively. These responses were associated with overflow of NPY-LI, which was similar to and threefold higher than that observed in controls at 2 and 10 Hz respectively, while no detectable overflow of NA occurred. Repeated stimulation with 10 Hz resulted in a progressive fatigue of the vasoconstrictor response and the associated overflow of NPY-LI, giving a high correlation (r = 0.86, P less than 0.001) between the two parameters. It is concluded that NPY is a potent constrictor of the renal vascular bed. Furthermore, although NA is the likely transmitter mediating most of the responses to low to moderate nerve activation under control conditions, the data suggest that NPY may mediate the non-adrenergic reductions in renal blood flow evoked by high-frequency sympathetic nerve stimulation after reserpine treatment.     

The influence of vascular β-adrenoceptors on the position and mobility of the rabbit incisor tooth

The influence of vascular β-adrenoceptors on the tooth-supporting functions of the periodontal ligament were studied in 30 anesthetized rabbits. Propranolol and the β₂-adrenoceptor antagonists ICI 118,551 and H 35/25 induced a marked extrusion of the incisor, probably due to reduced vasodilator tone in periodontal postcapillary blood vessels. Isoprenaline reversed the movement. β₁- and β₂-receptor antagonists decreased the intrusive responses to sympathetic nerve stimulation in teeth close to control position, but had no effect on responses in fully extruded teeth. Intrusive mobility, as tested by intermittent loading with 5–10 g, remained unaffected by β-adrenoceptor blockade. The results suggest that vascular β₂-adrenoceptors are important in the regulation of tooth position by their control of periodontal postcapillary resistance. Prejunctional β-receptors enhancing the vasoconstrictor - and intrusive - responses to sympathetic nerve stimulation are probably a mixture of β₁- and β₂-receptors. It would seem that the periodontal vasculature is important for the position of the rabbit tooth but, due to rapid adaptive mechanisms of the tooth-supporting tissues, the vasculature contributes little to the resistance against loadinduced intrusive movements of the tooth.     

Central hemodynamic effects of adrenaline with special reference to β2-adrenergic influence on heart rate and cardiac afterload in anesthetized cats

Central hemodynamic responses evoked by i. v.infusions of adrenaline and noradrenaline were studied in normovolemic anesthetized cats with intact adrenoceptors, after selective β₂-blockade (ICI 118,551), and after nonselective β-blockade (propranolol).The results demonstrated the presence of an important β₂-adrenergic component in the integrated response to ‘physiological’ doses of adrenaline contributing to increased cardiac output, decreased total peripheral resistance and virtually unchanged mean arterial blood pressure. Corresponding β₂-adrenergic effects of noradrenaline were small. The β₂-adrenergic effects of adrenaline on the heart seemed to be both direct and indirect. A moderate direct chronotropic response mediated by β₂-adrenoceptors apparently was present but there was no evidence of a direct β₂-adrenergic inotropic effect. An indirect, quite marked effect on the heart was accomplished by a β₂-adrenergic vasodilator interaction with the α-adrenergic vasoconstrictor influence on the systemic resistance vessels. This caused a net decrease in total peripheral resistance, thereby preventing an undue increase in cardiac afterload (arterial pressure) which seemed to be essential for evoking ‘optimal’ increases in cardiac output. It is suggested that such adrenaline evoked indirect, β₂-adrenergic improvement of cardiac performance is of functional importance in reflex sympatho-adrenal circulatory control.     

Classification of β-adrenoceptors in the microcirculation of skeletal muscle

Nervous and humoral β-adrenergic, postjunctional effects on microvascular resistance, on precapillary sphincter tone, and on transcapillary fluid exchange in cat skeletal muscle (Lundvall & Järhult 1974, 1976 a, Lundvall & Hillman 1978 a, b) were evaluated with regard to the β₁-or β₂,-specificity of the adrenoceptors. Marked β₂-dilator responses but no significant β₁-effects were observed. The conclusion was therefore reached that neurogenic as well as humoral β-adrenergic control of the microcirculation in skeletal muscle is exerted via activation of β₂-adrenoceptors.