Influence of renal denervation on vascular responsiveness of isolated rat intrarenal arteries

Microsurgical renal denervation of the rat has been reported to increase blood loss and bleeding time after a standardized kidney resection. To investigate the vascular effects of denervation, isolated intrarenal arteries were studied using sensitive 'isometric' recording equipment. Four pieces of evidence were obtained to indicate an effective functional denervation I week after renal nerve transection: (i) Phentolamine reduced the K+-induced contraction in controls but not in denervated arteries. (ii) The K+-induced contraction was significantly smaller in denervated than in control arteries. (iii) Noradrenaline (NA) was a significantly more potent vasoconstrictor (4 x) in denervated than in control arteries. (iv) Cocaine increased the NA sensitivity in control arteries (3 x), whereas it failed to do so in denervated vessels. Vasopressin, 5-hydroxytryptamine (5-HT), NA (in the presence of cocaine), prostaglandin F2 alpha (PGF2 alpha) and dopamine (DA) produced concentration-dependent contractions in the mentioned order of potency. Denervated arteries were found to be about two to three times more sensitive to the vasoconstrictors than control arteries. Angiotensin I and II had no contractile effect in any of the vessel segments examined. Indomethacin-pretreated arteries also failed to respond to angiotensin II. Neuropeptide Y produced only weak contractions and failed to influence the NA concentration-response relationship in either control or denervated arteries. In conclusion, renal denervation caused a general supersensitivity of the vascular smooth muscle cells to both circulating and non-circulating vasoconstrictors. Our results cannot explain the increased blood loss and bleeding time seen after denervation, but rather support the view that the enhanced bleeding was caused by an interrupted vasoconstrictor influence of the sympathetic nerves.     

Comparative effects of some calcium-channel blockers on human peripheral arteries and veins

We investigated the effects of five different calcium-channel blockers (CCBs), verapamil, nifedipine, diltiazem, flunarizine and lidoflazine, on contractions evoked in vitro by noradrenaline (NA) in small human arteries and veins from the epigastric region. Vessels were obtained from patients without obvious vascular diseases undergoing surgery because of inguinal hernias. The human superficial epigastric artery has previously been shown to contain mainly alpha 1-adrenoceptors, whereas in the vein alpha 2-adrenoceptors predominate. In experiments where NA (10(-5) M) was added non-cumulatively, it was found that nifedipine was the most potent relaxant agent in both arteries and veins, but that this drug showed no preference for any type of vessel. In contrast verapamil (10(-6) M) and (10(-5) M) diltiazem, flunarizine and lidoflazine inhibited the NA-induced contractions to a significantly greater extent in the arteries than in the veins. Comparison between diltiazem and nifedipine on contractions induced by cumulative addition to NA showed that both drugs had significantly more depressive effects on arteries than on veins if the vessels were contracted by relatively high concentrations of NA (10(-6) and 10(-5) M). The results thus confirm the clinical finding that CCBs have more pronounced effects on the arterial than on the venous side of the circulation. They do not support the view that CCBs are more effective inhibitors of alpha 2- than alpha 1-adrenoceptor mediated contraction in isolated human blood vessels.     

胎肝血管的解剖及其移植应用

目的观察胎肝的血管特点,探讨在临床带血管的胎肝移植的血管吻合的选择性。方法6～10个月胎龄的死胎33例于手术放大镜下原位解剖胎肝的附属血管,用直尺、卡尺和分割规测量附属血管的外径和长度。结果6～10个月胎龄的胎肝脐静脉的外径为(3.68±0.48)mm～(5.61±0.87)mm,长度为(36.12±4.58)mm～(50.97±7.68)mm;门静脉的外径为(2.31±0.43)mm～(4.16±0.65)mm,长度为(15.62±2.68)mm～(29.03±4.87)mm;肝固有动脉的外径为(1.67±0.82)mm～(2.32±0.98)mm,长度为(14.96±3.03)mm～(25.58±3.85)mm。脐静脉的外径较门静脉的外径粗(P<0.05);门静脉的外径较肝固有动脉的外径粗(P<0.05)。结论在胎肝移植前先结扎静脉导管,以脐静脉替代门静脉吻合,门静脉替代肝固有动脉吻合,更有利于吻合技术操作和供肝的双重血供,更有利于供肝发挥正常的功能。     

Effects of nifedipine on potassium-induced contraction and noradrenaline release in cerebral and extracranial arteries from rabbit

The present study was designed to evaluate the effects of the calcium antagonist nifedipine on potassium-evoked contractions and release of noradrenaline from sympathetic nerves in rabbit basilar and facial arteries. Contractions were measured isometrically in a small volume organ bath. While noradrenaline (NA) produced strong contractions in facial arteries, the majority of the basilar arteries responded only to the highest concentrations of NA employed (greater than 10 microM) with weak contraction. Prazosin (1 microM) and phentolamine (1-10 microM) effectively antagonized the responses to NA in both types of vessel. In contrast, contractions evoked by potassium (K+, 124 mM) were only slightly reduced by the alpha-adrenoceptor blocking agents, indicating that the participation of endogenous NA in maintaining the contractile response to K+ is either small or negligible in the vessel types studied. Nifedipine concentration-dependently inhibited K+-induced contractions in basilar and facial arteries, the former being significantly more affected as evidenced by the maximum inhibitions (approximately 80% compared to approximately 60%) and IC50 values (approximately 10 nM vs. approximately 30 nM). A combination of nifedipine (0.3 microM) and prazosin (1 microM) or phentolamine (1 microM) further suppressed the K+-evoked contractile response in facial arteries, but failed to do so in basilar arteries, when compared with the effect of nifedipine alone. The depressant effect of the alpha-adrenoceptor blockers was, however, still obtainable after reserpine treatment of the facial artery in vitro. Fluorescence histochemical demonstration of noradrenaline revealed a dense network of adrenergic nerve fibres in the walls of the basilar and facial artery. The vessels were also shown to accumulate 3H-NA and release it upon depolarization with K+. The uptake and subsequent release of 3H-NA were significantly reduced by desipramine (10 microM). Nifedipine (0.3-3.0 microM) failed to alter the K+-evoked 3H-NA efflux from sympathetic nerves in neither of the two vessel types. It may be concluded that nifedipine effectively inhibits K+-evoked contractions in isolated basilar and facial arteries from rabbit without interfering with nerve-mediated NA release. Possible explanations for this selective effect of nifedipine on muscle contraction are discussed.     

Mechanisms underlying pre- and postjunctional effects of neuropeptide Y in sympathetic vascular control

The effects of porcine neuropeptide Y (NPY) regarding sympathetic vascular control were studied in vitro on isolated rat blood vessels. The 10(-9)M NPY enhanced (about two-fold) the contractile responses to transmural nerve stimulation (TNS), noradrenaline (NA) and adrenaline (about two-fold) in the femoral artery. Higher concentrations of NPY (greater than 10(-8)M) caused an adrenoceptor-resistant contraction per se. The TNS-evoked [3H]NA efflux was significantly reduced by NPY in a concentration-dependent manner (threshold 10(-9)M). The calcium antagonist, nifedipine, abolished the contractile effects of NPY and the NPY-induced enhancement of NA contractions but did not influence the prejunctional inhibition of [3H]NA release. Receptor-binding studies showed that the ratio of alpha 1-to alpha 2-adrenoceptors in the femoral artery was 30:1. The NPY did not cause any detectable change in the number of alpha 1-or alpha 2-adrenoceptor binding sites or in the affinity of alpha 2-binding sites, as revealed by prazosin- and clonidine-binding, respectively. The NPY also inhibited the TNS-evoked [3H]NA release (by 42-86%) in the superior mesenteric and basilar arteries and in femoral and portal veins. The NPY still depressed TNS-evoked [3H]NA secretion from the portal vein in the presence of phentolamine. The NPY caused a clear-cut contraction in the basilar artery, increased the contractile force of spontaneous contractions in the portal vein, while only weak responses were observed in the superior mesenteric artery and femoral vein. The NA-induced contraction was markedly enhanced by NPY in the superior mesenteric artery, only slightly enhanced in the portal vein and uninfluenced in the femoral vein. In conclusion, in all blood vessels tested, NPY depresses the TNS-evoked [3H]NA secretion via a nifedipine-resistant action. Furthermore, NPY exerts a variable, Ca2+-dependent vasoconstrictor effect and enhancement of NA and TNS contractions.     

Postjunctional alpha 1- and alpha 2-adrenoceptors mediating contraction in isolated human groin arteries and veins

By means of selective agonists and antagonists for alpha 1- and alpha 2-receptors, the alpha-receptor subtypes in human groin arteries and veins were characterized and compared. In the arteries the alpha 1-receptor blocker prazosin caused a concentration-dependent parallel displacement of the noradrenaline (NA) concentration-response (cr) curve without reduction of maximum (pA2 = 9.86); the selective alpha 2-receptor antagonist rauwolscine in the concentration 10(-8) M caused a right-ward shift of the NA cr-curve without reduction of Emax, but 10(-7) M and 10(-6) M caused little or no further shift. In the veins, the two antagonists had the opposite effects. Rauwolscine caused a concentration-dependent right-ward shift of the NA cr-curve without depression of maximum (pA2 = 9.03); prazosin 10(-9) M significantly displaced the NA cr-curve, whereas 10(-8) M and 10(-7) M caused little or no further shift. The responses to the alpha 2-receptor agonist clonidine in the arteries were too small to allow calculations of pEC50 values; in the veins contractions were elicited in all vessel segments investigated (pEC50 = 6.24). Phenylephrine, selective for alpha 1-receptors, was significantly more potent in arteries than in veins. NA was significantly more potent in veins than in arteries. It is concluded that in human groin vessels, there is a functional predominance of alpha 1-receptors in the arteries and of alpha 2-receptors in the veins.     

Microvascular anatomy of the non-lobulated liver of adult Xenopus laevis: A scanning electron microscopic study of vascular casts

The microvascular anatomy of the non-lobulated liver of adult Xenopus laevis was studied by scanning electron microscopy of vascular corrosion casts. Hepatic portal veins and hepatic arteries entered hepatic lobes at the hiluses, hepatic veins left at these sites. Intraparenchymal, hepatic portal veins branched up to 10 times before terminal portal venules supplied liver sinusoids. Hepatic arteries closely followed portal vessels. Arteriolar side branches formed anastomoses with close by portal venules (arteriolar-portal anastomoses; APAs), liver sinusoids (arteriolar-sinusoidal anastomoses; ASAs), and peribiliary plexus vessels. Distally, hepatic arteries anastomosed with terminal portal venules having >100 μm in diameter. Liver sinusoids formed a dense three-dimensional network displaying signs of non-sprouting and sprouting angiogenesis evidenced by “holes” and blind ending tapering cast vascular structures (sprouts), respectively. Sinusoids drained via efferent hepatic veins. Right and left hepatic veins drained into the posterior caval vein. Locally, a dense honeycomb-like 3D-meshwork of resin structures was found around terminal portal venules and hepatic arteries. These networks were fed by hepatic arterioles and drained into adjacent terminal portal venules. As their morphologies differed significantly from sinusoids and they were found at sites where diffuse lymphoid tissue is described, we are convinced that they represent the vasculature of diffuse lymphoid tissue areas. Frequencies and diameter ratios of hepatic portal venules versus hepatic arterioles anastomosing with the former (APAs) implicate that the arterial supply contributes to the oxygenation of parenchymal and stromal cells rather than to a significant increase in blood flow towards hepatic sinusoids.     

Diameters of arteries, veins, and airways in isolated dog lung

Triple resin casts were made of the pulmonary arteries, veins, and airways from six dog lungs. The airways were cast at a pressure of 25 cm resin in all six. In the first three, both vessels were cast at a pressure of 30 cm resin, and in the second three, arteries were at 10 cm resin and veins at 5 cm resin. Measurements were made of luminal airway diameters down to 1 mm and of the luminal diameters of the corresponding segments of the vascular trees. The relation of one to the other was shown by calculating the regression lines for the corresponding diameters. Intrapulmonary arteries and veins are of approximately equal diameter when cast at 30 cm resin, while the veins are 20% larger than the arteries when cast at 5 cm and 10 cm of resin, respectively. Both vessel diameters are 75% of bronchial at the higher pressure, while at the lower pressures arteries are 59%, and veins 71% of bronchial. In any individual, vessel diameters are a relatively constant proportion of airway diameter. This constant of proportionality varies considerably between dogs, its value ranging from 0.48 to 1.03. It is concluded that in any individual all three trees have similar diameter ratios--that is, the ratio between mean diameters of branches in successive orders.     

Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease

Two nodules of hepatic adenomatous hyperplasia (AH) resembling focal nodular hyperplasia were found in two patients with cirrhosis or chronic active hepatitis. Imaging techniques suggested that the nodules were hepatocellular carcinoma. Pathological examination showed that the nodules (approximately 1.0 cm in diameter) were clearly demarcated from the surrounding liver tissue, and contained foci of scar-like fibrosis in the centre of the nodules. Microscopically, they contained portal tracts and fulfilled the criteria of AH. A large number of arteries were present in the central scarlike fibrosis as well as in the parenchyma of the nodules. There were foci of mildly atypical hepatocytes in one nodule but no cellular atypia in the other. Morphometric analysis showed that the cumulative luminal area of arteries per unit area was much greater in the nodules than in the extranodular liver tissues, while the cumulative luminal area of portal veins per unit area was much less in the nodules than in the extranodular liver tissues. Although the pathogenesis is unclear, these nodules might have developed through localized vascular changes associated with chronic liver disease, may have arisen from pre-existing arterial malformation, or may represent the early stages of angiogenesis in hepatocarcinogenesis.     

Modulation of vascular tone and reactivity by nitric oxide in porcine pulmonary arteries and veins

Isolated porcine pulmonary vessels were studied in order to evaluate the role of nitric oxide in arteries and veins. Leukotriene C4 and noradrenaline contracted porcine pulmonary arteries but induced only negligible contractions of porcine pulmonary veins. After treatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG), significant contractions to leukotriene C4 and noradrenaline were uncovered in pulmonary veins. In arterial preparations, L-NOARG caused a less marked potentiation of noradrenaline-induced contractions and did not alter leukotriene C4-induced contractions. Endothelium-dependent relaxations to acetylcholine were greater in veins compared with arteries whereas the endothelium-independent relaxations to the nitric oxide donor sodium nitroprusside (SNP) and the cyclic nucleotide analogue 8-bromo-cGMP were similar in the two preparations. Taken together these data suggest that the apparent insensitivity of porcine pulmonary veins to leukotriene C4 and noradrenaline was because of release of nitric oxide. The effect of nitric oxide synthase inhibition was less pronounced in porcine pulmonary arteries, suggesting a preferential functional role of nitric oxide in porcine pulmonary veins, originating in a greater production of nitric oxide by veins as opposed to arteries.     

Longitudinal Propagation of Myogenic Activity in Rabbit Arteries and in the Rat Portal Vein

Longitudinal spread of induced activity was analysed in the rat portal vein and rabbit aorta and compared to propagation in the brachial, radial, ear, mesenteric, femoral and posterior tibial arteries of the rabbit. Isometric force in spiral strips or intact preparations was measured during superfusion with Krebs' solution. The lower 20 per cent of the preparation could be selectively exposed to exogenous noradrenaline (NA) or to transmural field stimulation. Propagation was inferred to occur when the amplitude of the local response, relative to that when the entire preparation was stimulated, exceeded the relative length of the locally stimulated tissue. No propagation was found in the rabbit aortic strip. Propagation was less in proximal than in distal muscular arteries. The calculated distance of propagation was greatest in the rat portal vein. The intact limb vessel preparations reponded to NA with phasic contractions. In the ear artery, here was propagation only of the first phase of this biphasic response. These results show that different sections of the rabbit vascular tree display individuality in their ability to support propagation. In general, propagation in the arterial tree appears to be greatest in the smaller vessels.     

Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake and in vitro responses of 5-hydroxytryptamine

Immunocytochemical studies have revealed the presence of 5-HT-containing nerve fibres in all parts of the cerebrovascular bed (arteries, arterioles and veins) of mouse, rat, guinea-pig, rabbit and cat. Biochemical measurements (using HPLC) revealed substantial concentrations of 5-HT and 5-HIAA in the pial vessels of the rat, rabbit, cat and man, the amounts corresponding well with the density of the perivascular nerve supply. The uptake of 3H-5-HT was studied in arteries removed from the circle of Willis in rats. Maximum uptake was reached after 15 min of incubation at 37 degrees C and plateaued at 30 min. The reaction was temperature-dependent and found to be absent if performed at 0 degrees C. Pharmacological experiments on isolated middle cerebral and basilar arteries showed that vessels from rat and dog were contracted by approximately 90% upon administration of 5-HT, whereas vessels from guinea-pig, rabbit, cat and man were contracted by 40 to 60% relative to 124 mM K+. The EC50 values in the different species varied by between 1.5 X 10(-7) M (rat) and 3 X 10(-9) M (dog). The 5-HT-induced contractions were blocked by the 5-HT antagonists, methysergide, methergoline and ketanserin. Transmural nerve stimulation (TNS) of the rabbit basilar artery revealed a tetrodotoxin sensitive constriction whereas TNS of cat and dog middle cerebral arteries caused a tetrodotoxin-sensitive relaxation. The relaxation was not significantly attenuated until high doses of methergoline (3 X 10(-6) M) or ketanserin (3 X 10(-5) M) had been given.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pattern and distribution of intrahepatic lymph vessels in the rat

The pattern and distribution of intrahepatic lymph vessels were examined by light and electron microscopy in rat livers fixed by perfusion through the portal vein. Lymph vessels were found in the connective tissue of the larger portal canals, where they coursed in close association with branches of the hepatic artery. The smallest portal canals contained no lymphatics. Of the portal canals that lacked a lymphatic, over 50% also lacked an arterial component. Direct connections between the lymphatic lumen and the spaces of Disse or Mall were not observed but lymphatics were found close to Mall's space, separated by only a sparse connective tissue space containing a few collagen fibrils. Lymphatics were neither seen within the parenchyma, nor associated with intercalated (sublobular) veins. Cross-sectional area (223.2 +/- 48.7 micron2 SEM), maximum diameter (20.5 +/- 2.0 microns), volume density (0.00098 +/- 0.00046 micron3/micron3) and profile density (1.8 +/- 0.3 lymphatics per 1 mm2) of hepatic lymph vessels were determined by stereological measurement by a computer-based image analyzer. These data were used to estimate the rate of lymph formation in the liver. It was concluded that 1) initial lymphatics probably originate in the portal canals; 2) the concept that fluid in the space of Disse can be regarded as the principal source of fluid-forming hepatic lymph is questioned, since initial lymphatics appear to be separated from the space of Disse by hepatocytes and the space of Mall; and 3) the rate of lymph formation in the liver of the rat is approximately 0.06-0.08 microliter/min/cm2 of lymphatic endothelium.     

Characterization of two different calcium entry pathways in small mesenteric arteries from rat

The effects of Ca2+ removal, nifedipine, and La3+ on contractions induced by 124 mM K+ and 10 microM noradrenaline (NA) were investigated in small mesenteric arteries from rat. Ring segments of the arteries were suspended between two steel wires in a 2.5 ml muscle bath, and the mechanical activity recorded "isometrically". The tonic components of the contractile responses to both K+ and NA were critically dependent on the presence of Ca2+ in the bath solution. Nifedipine effectively relaxed K+-contracted arteries, whereas those activated by NA were considerably less affected by the drug. Application of NA to arteries depolarized by K+ in the presence of nifedipine induced a sustained tonic contraction, which was only approximately 20% smaller than that elicited by NA in "standard" Krebs solution, implicating pharmacomechanical coupling. Unlike nifedipine, La3+ inhibited K+- and NA-induced contractions to approximately the same extent. Re-application of Ca2+ to "Ca2+-depleted" preparations exposed to K+ and/or NA induced concentration-dependent contractions. The experimental results suggested that the effects of K+ and NA on the membrane permeability to Ca2+ were additive. The Ca2+-induced contractions were more inhibited by nifedipine in K+-depolarized than in NA-exposed arteries. It is concluded that K+ and NA utilize partly different Ca2+ entry pathways to increase the myoplasmic Ca2+ concentration in rat mesenteric arteries. Whereas K+ seems to promote the influx Ca2+ by activation of CA2+ channels sensitive to the membrane potential, the nature of the receptor-operated Ca2+ entry pathway remains to be established.     

Postjunctional α1- and α2-adrenoceptors mediating contraction in isolated human groin arteries and veins

By means of selective agonists and antagonists for α₁- and α₂-receptors, the α-receptor subtypes in human groin arteries and veins were characterized and compared. In the arteries the α₁-receptor blocker prazosin caused a concentration-dependent parallel displacement of the noradrenaline (NA) concentration-response (cr) curve without reduction of maximum (pA₂=9.86); the selective α₂-receptor antagonist rauwolscine in the concentration 10^-8 M caused a right-ward shift of the NA cr-curve without reduction of E_max, but 10^-7 M and 10^-6 M caused little or no further shift. In the veins, the two antagonists had the opposite effects. Rauwolscine caused a concentration-dependent right-ward shift of the NA cr-curve without depression of maximum (pA₂=9.03); prazosin 10^-9 M significantly displaced the NA cr-curve, whereas 10^-8 M and 10^-7 M caused little or no further shift. The responses to the α₂-receptor agonist clonidine in the arteries were too small to allow calculations of pEC50 values; in the veins contractions were elicited in all vessel segments investigated (pEC₅₀=6.24). Phenylephrine, selective for α₁-receptors, was significantly more potent in arteries than in veins. NA was significantly more potent in veins than in arteries. It is concluded that in human groin vessels, there is a functional predominance of arreceptors in the arteries and of a2-receptors in the veins.     

Influence of extracellular calcium and nifedipine on alpha 1- and alpha 2-adrenoceptor-mediated contractile responses in isolated rat and cat cerebral and mesenteric arteries

The influence of extracellular Ca2+ and nifedipine on contractile responses to 10 microM noradrenaline (NA) was investigated in isolated rat and cat middle cerebral (RCA, CCA) and mesenteric (RMA, CMA) arteries. In the CCA (containing predominantly alpha 2-adrenoceptors), the NA-induced contractions developed considerably more slowly than in the RCA, RMA (containing mainly alpha 1-adrenoceptors) and CMA (sensitive to both alpha 1- and alpha 2-adrenoceptor selective antagonists). The tonic component of the NA-induced contraction in the four types of artery was substantially suppressed after only short periods in Ca2+-free solution. In each type of artery, excluding the CCA, the contractile response to 124 mM K+ was more sensitive to Ca2+ deprivation than that to NA. This suggests that NA, besides mobilizing extracellular Ca2+, can also release Ca2+ from an intracellular pool in the RCA, RMA and CMA, but not in the CCA. Thus, alpha 1-adrenoceptor-mediated contractions in the RCA and RMA seem to depend on both Ca2+ influx and intracellular Ca2+ release, whereas alpha 2-adrenoceptor-mediated contractile responses in the CCA appear to rely almost entirely on Ca2+ influx. Both the maximum response and the tonic component of the NA-induced contraction were significantly more sensitive to nifedipine in the CCA than in the RCA. In comparison with the NA-induced contractions in these arteries, those in the RMA and CMA were relatively resistant to nifedipine. In the CCA exposed to NA in Ca2+-free medium, nifedipine almost abolished the contraction induced by re-addition of Ca2+, whereas in the other types of artery, Ca2+ re-application evoked a significant contraction also in the presence of the drug. The differential effects of nifedipine presumably reflect differences between the arteries, not only in the relative contribution of Ca2+ influx and intracellular Ca2+ release to the contractile activation, but also in the nifedipine sensitivity of the Ca2+ entry pathways utilized by NA. It is concluded that the mechanisms through which NA induces contraction seem to be related both to the subtype of alpha-adrenoceptor stimulated by NA and to the type of vessel studied.     

Neuropeptide Y: Immunocytochemical localization to and effect upon feline pial arteries and veins in vitro and in situ

Plexuses of nerve fibres containing neuropeptide Y (NPY)-like immunoreactivity invest pial arteries belonging to the circle of Willis, pial arterioles, occasionally penetrating arterioles and large veins. A more sparse supply of NPY-like fibres are observed around pial veins and venules. The NPY-immunoreactive fibres are located within the adventitia or at the adventitia-media border. Only occasional fibres are present in cerebral vessels of animals in which the superior cervical ganglion has been removed one week previously. Administration of NPY resulted in strong, concentration-dependent contractions of isolated feline middle cerebral arteries whereas administration of avian pancreatic polypeptide (APP) elicited weak contractions. In chloraloseanaesthetized cats, perivascular microapplication of NPY in situ resulted in marked concentration-dependent contractions of cerebral pial arterioles (34.7±6.6%; maximum decrease in calibre with NPY. Perivascular administration of NPY resulted in the constriction of pial veins but the magnitude of the venous calibre reductions was smaller than the response of arterioles at each reductions was smaller than the response of arterioles at each concentration examined. APP did not elicit contraction of pial arterioles or veins during in situ conditions. The pharmacological and immunocytochemical results strongly indicate the existence of a novel perivascular neuronal system containing NPY, which mediates contraction of cerebral blood vessels and NPY is colocalized with NA in sympathetic nerves.     

Contractile effects of noradrenaline and 5-hydroxytryptamine in human hand veins: a pharmacological receptor characterization

The postjunctional receptors mediating contractile responses to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were characterized in ring segments of human hand veins by using subtype selective agonists and antagonists. The mechanical characteristics of the preparations were also examined by length-tension measurements. The length-active wall tension curve was bell-shaped and reached a maximum at a length corresponding to a passive distending pressure of approximately 14 mmHg. (-)-Phenylephrine consistently contracted the veins and was 24 times less potent than (+/-)-NA whereas clonidine produced a contraction in only two out of 11 vessel segments. Neither prazosin nor rauwolscine competitively inhibited the contractile response to NA, and large inter-individual differences were found in the degree of inhibition produced by the antagonists. However, application of both prazosin and rauwolscine almost abolished the NA-induced contraction. Ketanserin and methergoline inhibited the contractile response to 5-HT; the former in an apparently competitive manner with a pA2 value of 8.94, whereas the latter substantially reduced the maximum 5-HT response. It is suggested that NA elicits contraction in human hand veins by acting at a mixed population of alpha 1- and alpha 2-adrenoreceptors. The contractile response to 5-HT, on the other hand, appears to be mediated predominantly by 5-HT2 receptors.     

Pharmacological characterization of postjunctional alpha-adrenoceptors in isolated human omental arteries and veins

The alpha-adrenoceptors in human omental arteries and veins were characterized and compared. In the arteries both prazosin (pA2 9.48) and rauwolscine (pA2 7.19) displaced the noradrenaline (NA) concentration-response (cr) curve towards higher concentrations without reduction of maximum. Neither clonidine, nor oxymetazoline had any consistent contractile effects. Phenylephrine had a lower potency than NA, but a similar intrinsic activity. In the veins, both prazosin (pA2 9.72) and rauwolscine (pA2 8.11) displaced the NA cr-curve towards higher concentrations, but also significantly depressed maximum. Clonidine and oxymetazoline contracted veins from 3 out of 7 and 4 out of 6 patients, respectively. Their pD2-values were similar to that of NA, but their intrinsic activities were significantly lower. NA was more potent than phenylephrine in these vessels, and there was no significant difference in intrinsic activity. The results suggest that in human omental arteries, the postjunctional alpha-adrenoceptors are mainly of the alpha 1-type, even if a small population of alpha 2-adrenoceptors cannot be excluded. In omental veins, there seems to be a functionally important population of postjunctional alpha 2-adrenoceptors occurring together with a population of alpha 1-adrenoceptors.     

Relaxant and contractile effects of some amines and prostanoids in myometrial and vascular smooth muscle within the human uteroplacental unit

Tissue specimens of human myometrium and placenta were obtained at caesarean section and normal vaginal deliveries. Strips of myometrial tissue, and segments of intramyometrial arteries, chorionic plate arteries and veins, and stem villous arteries were dissected. The preparations were mounted in organ baths, and isometric tension was recorded. In myometrial preparations, prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), noradrenaline (NA) and serotonin (5-HT) all caused concentration-related contractions. In vascular preparations, the maximum contractant or relaxant effect, Emax or Imax, and the drug concentrations causing half maximum responses, EC50 or IC50 were determined. In intramyometrial arteries no significant differences between Emax or EC50 values were found for NA, 5-HT and PGF2 alpha. The Imax values (relaxation of vessels contracted by vasopressin) ranged prostacyclin (PGI2) greater than PGF2 alpha = PGE2, and the IC50 values PGF2 alpha = PGE2 = PGI2 (PGF2 alpha less than PGI2). Thus, PGF2 alpha showed dual effects. Only PGI2 relaxed placental vessels contracted by PGF2 alpha. In chorionic arteries, Emax values ranged PGE2 = PGF2 alpha greater than 5-HT greater than NA, and IC50 values 5-HT less than NA = PGF2 alpha = PGE2. In stem villous arteries, Emax ranged PGE2 = PGF2 alpha greater than 5-HT = NA, and EC50 5-HT = NA = PGE2 = PGF2 alpha. In chorionic veins the order of Emax values was PGF2 alpha = PGE2 greater than 5-HT greater than NA, and that of the EC50 values 5-HT less than NA = PGF2 alpha = PGE2. Smooth muscle tissues from the human uteroplacental unit show individual responses to prostanoids and amines, probably reflecting individual mechanisms for control of contractile activity and blood flow.