Myointimal hyperplasia and sympathetic reinnervation following local cold injury and rapid rewarming in the rabbit central ear artery

BACKGROUND: Functional and pathological improvements following rapid rewarming in 42 degrees C water was compared with alterations following slow thawing at room temperature (22 degrees C) after frostbite (-9 degrees C, 15 minutes) in vivo of the rabbit central ear artery. METHODS: Following two to ten weeks of in vivo regeneration, vascular segments were tested in vitro. Maximal and dose-dependent isometric contractions were induced by exogenous noradrenaline. Sympathetic nerves in the vascular wall were stained with glyoxylic acid. Vascular ring segments were stained with haematoxylin and eosin. RESULTS: Following slow thawing, the total uptake, the K+ evoked and the spontaneous release of [3H]noradrenaline in the sympathetic nervous system were strongly reduced two weeks after freezing, with a subsequent increase to control level within 3-4 weeks. After rapid rewarming the total uptake, the spontaneous release and the K+ evoked release of [3H]noradrenaline commenced earlier such that after ten weeks the level was twice as high as following slow rewarming. The glyoxylic acid induced catecholamine fluorescence in sympathetic nerves, revealed an earlier regeneration after rapid rewarming. Haematoxylin and eosin-stained segments revealed less intimal hyperplasia three to 20 weeks after rapid rewarming than after slow thawing. CONCLUSION: Rapid rewarming of in vivo frozen arteries in warm water (42 degrees C) did not prevent immediate vasoparalysis and degeneration of sympathetic nerves. However, nerve regeneration occurred earlier and with higher tissue nerve densities as compared to tissue that had been slowly rewarmed. Myointimal hyperplasia was less pronounced after rapid rewarming. Abnormal sympathetic nerve function and myointimal hyperplasia, as observed in this study, may contribute to a greater understanding of sequelae in the human body following frostbite.     

Neurotransmitter release and vascular reactivity in spontaneously hypertensive rats

This study was designed to investigate neurotransmitter release during the sympathetic nerve stimulation of perfused mesenteric arterial beds of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) at young and adult ages. The role of Ca in neurotransmitter release and vascular responsiveness was also examined by using a Ca-antagonist (verapamil). Pressor responses to electrical nerve stimulation and exogenous noradrenaline were greater in SHR than in WKY. Noradrenaline overflow by electrical nerve stimulation from mesenteric arterial beds was also significantly greater in young SHR than age-matched WKY. However, in adult SHR, the noradrenaline overflow was reduced compared with WKY. After verapamil infusion (5.0 X 10(-7)M approximately 2.5 X 10(-6)M), suppression of the pressor responses and noradrenaline overflow evoked by electrical nerve stimulation was greater in SHR than in WKY at both ages. The pressor responses to exogenous noradrenaline were also inhibited by verapamil more in young SHR than in young WKY. In adult SHR, the inhibition was similar to age-matched WKY. These results suggest that noradrenaline release from sympathetic nerve endings in SHR increase at a young age and decreases in adults, and depends at least partly on Ca-influx at both ages as dose vasoconstrictor reactivity. Therefore, Ca-dependency in SHR at both pre- and post-synaptic sites of neurotransmission may contribute to the pathogenesis of hypertension.     

Changes in the vascular reactivity of the isolated tail arteries of spontaneous and renovascular hypertensive rats to endogenous and exogenous noradrenaline

We have investigated the changes in the responses to noradrenaline of isolated tail arteries of spontaneously hypertensive (SHR) and renovascular hypertensive rats (Wistar-Kyoto: two-kidney, one-clip model, WKY:2K1C) compared with normotensive (Wistar-Kyoto, WKY) rats. Renovascular hypertension was induced by 4 weeks' unilateral renal artery clipping. Arteries were vasoconstricted with exogenous noradrenaline, electrical field stimulation or high potassium. The effects of the latter two stimuli were abolished by reserpine and so were presumably dependent on the presence of endogenous noradrenaline. In the SHR the maximal vasoconstriction produced by all three stimuli was greater than in WKY. Dose-response curves were steeper and there was no change in threshold. Vascular mass was greater. We interpret these results as showing an increase in vascular reactivity in the SHR caused by structural adaptation. The WKY:2K1C responses to noradrenaline could also be explained in terms of structural adaptation but there was no increase in vascular mass. Sensitivity to potassium and electrical stimulation was decreased, suggesting a defect in vascular neurotransmission. This was supported by the observations of a decreased arterial noradrenaline content and of decreased sensitivity to cocaine.     

Peripheral sympatholytic actions of four AT1 antagonists: are they relevant for long-term antihypertensive efficacy?

BACKGROUND: Angiotensin II causes hypertension not only by direct constriction of vascular smooth muscle, but also by facilitating the release of noradrenaline from sympathetic terminals and by enhancing vascular noradrenaline sensitivity. AT1 receptor antagonists attenuate all these actions, but display some evidence of substance-related selectivities. OBJECTIVE: The contribution of pre- or postsynaptic impairment of sympathetic transmission to long-term antihypertensive efficacy should be determined for four structurally different, clinically approved AT1 antagonists. DESIGN: Spontaneously hypertensive rats were treated with candesartan, eprosartan, irbesartan, or losartan via osmotic minipumps for 4 weeks at doses yielding identical reductions of blood pressure. Maximum efficacy was obtained with a tripled dose of candesartan. METHODS: In the pithed rat model, stimulus/response dependencies were determined for vasopressor effectivity of preganglionic electrical stimulation, and of intravenous bolus applications of noradrenaline and angiotensin II. RESULTS: Losartan, irbesartan, eprosartan, and candesartan at doses of 5, 40, 20, and 0.05 mg/kg per day, were equally effective in reducing basal systolic blood pressure (-42 mmHg), and the vasopressor potency of angiotensin II (approximately 10-fold). The efficacies of preganglionic stimulation and exogenous noradrenaline were unaltered, with the exception of irbesartan, which reduced vascular noradrenaline sensitivity. The tripled dose of candesartan further reduced basal and angiotensin II-stimulated blood pressures, and significantly attenuated vascular noradrenaline sensitivity. CONCLUSION: AT1 antagonists at doses that effectively reduce blood pressure in chronic therapy do not generally suppress peripheral sympathetic function. A potential interaction consists in a reduction of vascular noradrenaline sensitivity, which can be considered as a class effect of AT1 antagonists at high dosage.     

Uptake of 125I-triiodothyronine by the thyroid gland: effect of adrenergic agents and low temperatures

A study was made of the binding of 125I-triiodothyronine with the sections, nuclei and mitochondria of the euthyroid thyroid under the conditions of adding adrenergic agents, cooling to 0 degree C and freezing to--196 degrees C. It was noted that 125I-T3 got no less with adding unlabeled T3 and thyroxine that might suggest the unsaturated nature of the process. Among the studied adrenergic agents (noradrenaline, neoepinephrine, propranolol, pyrroxane in the concentration of 1 X 10(-4) M) noradrenaline only influenced this process. It stimulated binding and pyrroxane inhibited it. 125I-T3 binding got less at 0 degree C, after freezing to--196 degrees C the preservation of the basal activity of the process and disappearance of the noradrenaline stimulating effect were noted. The results obtained do not confirm assumptions as to the mechanism of thyroid autoregulation function with T3 by the short feedback type.     

The Role of Calmodulin in Neurotransmitter Release and Vascular Responsiveness in Spontaneously Hypertensive Rats

ABSTRACT

This study was designed to investigate the role of calmodulin in adrenergic transmission in hypertension. In perfused mesenteric vasculature: from spontaneously hypertensive rats(SHR, 7-9 weeks of age) and age-matched Wistar Kyoto rats(WKY), the effects of a specific calmodulin antagonist(W-7) on norepinephrine overflow and vascular responsiveness to endogenous and exogenous norepinephrine were examined.

The vasoconstrictor responses to electrical nerve stimulation and exogenous norepinephrine as well as norepinephrine overflow during electrical nerve stimulation were significantly enhanced in SHR compared with those in age-matched WKY. The calmodulin antagonist, W-7, reduced not only vasoconstrictor responses but also norepinephrine overflow during nerve stimulation. These inhibitory effects of W-7 were significantly greater in SHR than in WKY.

The results demonstrate that norepinephrine overflow from the sympathetic nerve endings and vascular responsiveness were increased in SHR. The marked reduction in norepinephrine overflow and pressor responses by W-7 might suggest the greater calmodulin-dependent adrenergic transmission in this model of hypertension.     

Myocardial potassium uptake and catecholamine release during cardiac sympathetic nerve stimulation

To determine whether sympathetic nerve stimulation induces a significant potassium uptake in the myocardium, the changes in myocardial potassium balance, catecholamine release, lactate uptake, and oxygen consumption were recorded in eight anaesthetised open chest pigs during electrical stimulation of the right intermediate cardiac nerve at 10 Hz. Potassium concentrations were continuously measured by polyvinylchloride valinomycin minielectrodes in arterial and coronary sinus blood. Potassium concentration in coronary sinus blood fell to a nadir 0.42(0.21-0.61) mmol.litre-1 below control values (median and 95% confidence interval) and resulted in a peak potassium uptake of 65(38-102) mumol.min-1 100 g-1 after 2.5(2.0-3.0) min, which correlated (r = 0.94, p less than 0.001) with cardiac noradrenaline release. Accumulated myocardial potassium uptake amounted to 139(82-241) mumol.100 g-1 when a stable potassium concentration difference between arterial and coronary sinus blood was reached after 5.5(4.25-6.50) min. Cardiac contractility (LV dP/dt), myocardial oxygen consumption, and lactate uptake rose from control to peak potassium uptake (p less than 0.001) by 140%, 158%, and 92% respectively. Coronary sinus blood noradrenaline and adrenaline concentrations rose significantly (p less than 0.01) from 58(44-87) pg.ml-1 at control to 2208(1159-5627) pg.ml-1 at peak uptake and from 15(11-19) pg.ml-1 to 85(64-230) pg.ml-1 respectively. Arterial noradrenaline increased from 29(19-41) pg.ml-1 to 374(176-640) pg.ml-1 and arterial adrenaline rose from 15(11-23) pg.ml-1 to 31(24-52) pg.ml-1 (p less than 0.001). It is concluded that sympathetic nerve stimulation induces a substantial myocardial potassium uptake in a dose dependent relation to cardiac noradrenaline release and alters the contractile and metabolic state of the heart substantially with only minor changes in arterial catecholamine concentration.     

Release of endogenous catecholamines in the ischemic myocardium of the rat. Part B: Effect of sympathetic nerve stimulation

The contribution of centrally originating sympathetic activity to the myocardial extracellular accumulation of noradrenaline during the early phase of ischemia has been assessed in a perfused (Langendorff) rat heart preparation isolated except for its sympathetic innervation. A 10-minute electrical stimulation (4 Hz, 5 V) of the left cervicothoracic ganglion during normal perfusion causes the overflow of 177.5 +/- 13.7 pmol noradrenaline/g heart, whereas such stimulation during ischemia liberates only 21.5 +/- 3.6 pmol/g (collected during reperfusion). When neuronal reuptake is blocked by desipramine, corresponding values are 321.5 +/- 22.5 pmol/g (normal flow) and 151.8 +/- 22.4 pmol/g (ischemia). After combined blockade of neuronal uptake, extraneuronal uptake, and alpha 2-receptors, nerve stimulation liberates 674 +/- 22 pmol/g during normal flow and 206 +/- 24.3 pmol/g during ischemia. These results suggest that, in vivo, centrally originating neural activity would not lead to substantial accumulation of noradrenaline within the extracellular space of the ischemic myocardium. This failure of accumulation is due to both a functioning neuronal uptake of noradrenaline and a failure of neurotransmission.     

Chronic hyperinsulinemia enhances adrenergic vasoconstriction and decreases calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats.

The present study investigated the influence of chronic hyperinsulinemia on vascular responsiveness induced by adrenergic nerves and calcitonin gene-related peptide-containing (CGRPergic) nerves in pithed rats with insulin resistance. Male Wistar rats (6 weeks old) received 15% fructose solution in drinking fluid for 10 weeks (fructose-drinking rats: FDR), which resulted in significant increases in plasma levels of insulin, total cholesterol and triglyceride, and systolic blood pressure, as compared with control rats. Pithed FDR showed greater adrenergic nerve-mediated pressor response to spinal cord stimulation (SCS) at the lower thoracic vertebra (Th 9-12) and pressor response to exogenous noradrenaline than control rats. In pithed FDR with blood pressure artificially increased by continuous infusion of methoxamine and blockade of autonomic ganglia by hexamethonium, CGRPergic nerve-mediated depressor responses to SCS were significantly smaller than those in control rats, but depressor responses to other vasodilators such as acetylcholine, CGRP and sodium nitroprusside were similar to those in control rats. These results suggest that chronic hyperinsulinemia in FDR facilitates adrenergic nerve-mediated vasoconstriction, which is associated with attenuated CGRPergic nerve-mediated vasodilation.     

Increased sensitivity to noradrenaline in glucocorticoid-treated rats: the effects of indomethacin and desipramine

Vascular responsiveness was evaluated in perfused mesenteric arteries from rats infused with dexamethasone (2 micrograms/day). Full dose-response curves to noradrenaline, vasopressin and potassium chloride were established. In order to investigate whether prostaglandins or noradrenaline uptake were involved in dexamethasone-induced pressor changes, vascular responses were compared before and during treatment with either indomethacin (a cyclo-oxygenase inhibitor) or desipramine (an inhibitor of neuronal catecholamine uptake). Dexamethasone-treated tissues showed an increased vascular sensitivity to noradrenaline compared with controls; the maximal response was greater and the concentrations of agonist required for a 50% response (EC50) was less in dexamethasone-treated tissues. The responses to vasopressin and potassium chloride were not affected. Systolic blood pressure in dexamethasone-treated rats was not significantly different from that in controls. Indomethacin infusion decreased the vascular responsiveness to noradrenaline in control and dexamethasone-treated rats to a similar degree. Noradrenaline responses after indomethacin treatment were not significantly different in control and dexamethasone-treated tissues. 6-Keto-prostaglandin-F1 alpha output during stimulation with noradrenaline was not affected by dexamethasone. Desipramine lowered pressor responses to noradrenaline at all concentrations and decreased the maximal response in tissues from dexamethasone-treated but not control rats. However, during infusion with desipramine, the EC50 for noradrenaline after dexamethasone was still less than in controls. Dexamethasone at low doses appears to selectively increase vascular sensitivity to noradrenaline in rats at a prehypertensive stage by changing prostaglandin synthesis and, possibly, neuronal uptake of noradrenaline.     

Survival of calcium pyrophosphate crystals in stored synovial fluids.

Eleven synovial fluids containing calcium pyrophosphate dihydrate (CPPD) were examined repeatedly over an eight week period to assess whether storage conditions and duration influenced the number of crystals present. Aliquots of each fluid were stored at room temperature, 4 degrees C, and -70 degrees C. At -70 degrees C there was no change in crystal count after eight weeks' storage. At room temperature and 4 degrees C crystal counts declined slowly over the eight week period, though CPPD crystals were still readily apparent after eight weeks in 10/11 (4 degrees C) and 8/11 (room temperature) fluids. No change in crystal morphology was detected and, apart from one fluid kept at room temperature in which fungal hyphae were noted at six weeks, no new crystals were seen. Calcium pyrophosphate dihydrate crystals in synovial fluid can be maintained for prolonged periods by freezing.     

Axonal transport of noradrenaline and noradrenergic transmission in rats with streptozotocin-induced diabetes

Summary The accumulation of noradrenaline in constricted sciatic nerves was measured in 6 month diabetic rats (streptozotocin 35 mg/kg) and 4 day diabetic rats (streptozotocin 70 mg/kg) together with two groups of age-matched control animals. There was no alteration in the amount of noradrenaline accumulated in the nerves of the diabetic animals when compared with the controls. The vasa deferentia of the long-term diabetic animals showed an impaired response to stimulation of their noradrenergic nerves and a hypersensitivity to exogenous noradrenaline. These vasa were not wasted and showed a normal contractility in response to potassium chloride. Vasa deferentia from the short-term diabetic rats showed no abnormalities of function. Vasa deferentia from all groups of rats were also examined at the ultrastructural level. Specimens from all the chronically diabetic animals contained many abnormal nerve terminals. These lesions were not seen in vasa from the shortterm diabetic rats. Taken together these findings indicate that rats with chronic streptozotocin-induced diabetes exhibit pathological changes in the noradrenergic nerves supplying the vas deferens. These animals do not, however, show an impairment of the axonal transport of noradrenaline.     

Noradrenergic afferents facilitate the activity of tuberoinfundibular neurons of the hypothalamic paraventricular nucleus

The role of ascending noradrenergic projections of medullary origin in regulating the activity of tuberoinfundibular neurons of the hypothalamic paraventricular nucleus (PVN) was examined in pentobarbital-anesthetized male Sprague-Dawley rats. Discrete electrical stimulation of either the A1 or the A2 noradrenaline cell group areas of the caudal medulla enhanced the probability of firing in a substantial proportion of antidromically identified tuberoinfundibular PVN cells tested. Notably, no inhibitory effects were observed. Destruction of the PVN noradrenergic terminal plexus by local application of the neurotoxin 6-hydroxydopamine 1 day prior to electrophysiological experiments abolished the effects of both A1 and A2 stimulation. These findings indicate that noradrenergic afferents can exert a facilitatory influence on the activity of a population of tuberoinfundibular PVN neurons, thus supporting earlier suggestions that central noradrenergic structures can enhance the release of certain anterior pituitary hormones.     

VEGF对血管内皮细胞损伤的拮抗作用及作用机制

冻结性冷损伤是以组织冻结再融化过程的病理改变为基础的损伤。已经证实,血管内皮细胞（VECs）除有屏障和膜转运功能外,还具有内分泌功能,主动参与了多种生命活动,对维持体内环境的平衡与稳定具有重要作用。冻伤过程中VECs的损伤,可促进微循环血栓形成造成微循环障碍;待到复温后,血液恢复流动又可导致不可逆的再灌注损伤。因此,减轻内皮细胞损伤,可以减少微循环血栓形成,从而减轻再灌注对机体造成的损伤。血管内皮细胞生长因子（VEGF）作为重要的血管生长因子,在冻伤时对VECs损伤具有拮抗作用,可通过促进血管再生、抗血栓形成、抑制血管平滑肌过度生长及抗炎的作用等实现的对血管的保护作用,为临床防治冻伤提供了新的思路。     

Survival and infectivity of Brugia malayi microfilariae after cryopreservation

Methods were studied for the cryopreservation of microfilariae of periodic Brugia malayi. RPMI-1640 tissue culture medium containing 6% dimethyl sulfoxide (DMSO) and 15% newborn calf serum was used as cryoprotectant. Samples were frozen slowly in the vapor phase of liquid nitrogen prior to emersion in liquid nitrogen (-196 degrees C). The freezing rate was -0.5 to -1.0 degrees C per minute, microfilariae remained viable for as long as, 212 and 375 days, survival rates were 94 to 98% and they were infective to Aedes togoi mosquitos. The infective larvae (L3) were obtained for 10-11 days after feeding at 28 degrees C room-temperature and the infection rate of L3 in test mosquitos was 22.4-30.6%. All DMSO should be removed from the freezing medium to restore microfilariae activity after freezing.     

Attenuation of lipopolysaccharide-induced hyperreactivity of human internal mammary arteries by melatonin

Reactive oxygen species (ROS) are thought to be important mediators in ischaemia/reperfusion injury following coronary vasospasm. The most ubiquitous action of melatonin is that of a free radical scavenger. Therefore, we investigated the action of melatonin by monitoring changes in the tone on ring preparations from human internal mammary arteries (IMA). In quiescent IMA rings melatonin (0.1 nm-10 microm) never elicited any change in baseline tension but 1-100 nm melatonin enhanced significantly maximal responses to noradrenaline (NA) in arteries with endothelial function. In NA (1 microm) precontracted arteries inhibition of nitric oxide (NO(*)) formation by N(G)-monomethyl-L-arginine (l-NMMA, 100 and 400 microm) eliminated 43 +/- 7 and 61 +/- 7% of the acetylcholine (ACH) effect. Melatonin (100 and 400 nm) attenuated maximal endothelium-dependent relaxant responses to ACH slightly by 23 +/- 9 and 17 +/- 9% leaving responses to direct stimulation of soluble guanylate cyclase by sodium nitroprusside unchanged. Incubation of IMA for 20 hr at 37 degrees C with 1 microg/mL lipopolysaccharide (LPS) enhanced maximal NA effects to 147 +/- 18% (n = 22, P < 0.01) whereas 50 microg/mL LPS reduced the NA maxima to 68 +/- 9% (n = 10, P < 0.01) of the control effects. The LPS-induced potentiation was completely attenuated by coincubation with melatonin (400 nm) and significantly reduced by coincubation with the thromboxane synthase inhibitor dazoxiben (10 microm). It is suggested that the LPS-induced hyperreactivity of vascular smooth muscle is mediated through enhanced release of ROS and prostanoids and that melatonin inhibits the vascular hyperreactivity through selective scavenging of ROS.     

Interaction between neuronal amine uptake and prejunctional alpha-adrenergic receptor activation in smooth muscle from canine blood vessels and spleen.

Experiments were performed to determine the conditions in which norepinephrine release from adrenergic nerve terminals in smooth muscle from canine blood vessels and spleen might be inhibited by prejunctional alpha-adrenergic receptor activation. Strips of aorta, mesenteric and splenic arteries, splenic capsule and portal and saphenous veins were labeled with 7-3H-norepinephrine and mounted for superfusion. In the portal vein, an inhibitory effect of prejunctional receptor activation with exogenous norepinephrine (1.2 X 10(-6) M) on transmitter efflux could be demonstrated during electrical stimulation (9 V, 2 Hz) of the nerve terminals. By contrast, in the other tissues, inhibition of transmitter release during electrical stimulation or depolarization of the nerve terminals with K+ (40 mEq/l) could only be demonstrated aftet blockade of the neuronal uptake mechanism. That activation of prejunctional alpha-adrenergic receptors in blood vessels inhibits the exocytotic process is suggested by the failure of exogenous norepinephrine to affect either the basal efflux of 3-H-norepinephrine or the displacement of 3H-norepinephrine by tyramine.     

Stability of coagulation proteins in frozen plasma.

This study reports on the frozen stability of all commonly measured coagulation proteins in normal citrated plasma: activated partial thromboplastin time, prothrombin time (%), thrombin time and fibrinogen (Clauss); clotting assays for factors II, V, VII, VIII, IX, X, XI and XII; functional assays for protein C (clotting), protein S (clotting), antithrombin (chromogenic) and plasminogen (chromogenic); and immunological assays for von Willebrand factor and D-dimer. All these factors listed are stable for up to 3 months if frozen at -24 degrees C or lower. At -74 degrees C, all these factors (allowing for 10% variation) were stable for at least 18 months, most were stable for 24 months. The number of proteins showing > 5% variation over baseline after 6 months storage indicates that some decay does occur even at -74 degrees C. There was no clear advantage in snap freezing at -74 degrees C and then storing at -24 degrees C over both freezing and storing at -24 degrees C; therefore, the freezing process itself is not responsible for the loss of stability. The best stability, especially at -24 degrees C, was obtained when small samples (1 ml) were stored in screw-cap tubes with a minimum dead space. The decrease in stability of the coagulation proteins directly correlates with the effect of temperature and time.     

Homologous and heterologous regulation of atrial natriuretic factor receptors in smooth muscle cells

Two subtypes of atrial natriuretic factor (ANF) receptors are present in vascular smooth muscle cells: B(biologically active) receptors coupled to a guanylate cyclase and C (clearance) receptors (95 per cent of the total number of ANF binding sites) non coupled to any identified second messenger system. We compared the homologous receptor regulation induced by ANF to the heterologous one elicited by angiotensin II (Ag II). Binding of (3-[125I]iodotyrosyl) rat ANF and cGMP production stimulated by ANF were measured after 18 hours preincubation of rat cultured vascular smooth muscle cells (10(6) cells/dish) at 37 degrees C with ANF or Ag II. The hormones (10 nM) decreased to the same extent the total apparent number of ANF binding sites (control: 208 +/- 25 fmol/10(6); ANF : 82 +/- 20 fmol/10(6) cells; Ag II : 90 +/- 9 fmol/10(6) cells) The diminution of the number of ANF binding sites induced by ANF exposure was reversed by 85 per cent following 10 minutes treatment of the cells with 10 mM AcOH. Moreover, treatment with ANF (10 nM) led to a diminution of cGMP stimulation induced by ANF, this effect being still present after washing the cells with 10 mM AcOH. In contrast, diminution of ANF building sites consecutive to Ag II exposure was not affected by AcOH treatment and a potentiation of cGMP production elicited by ANF was observed. These results suggest that, in rat vascular smooth muscle cells, B receptors are sensitive to homologous down regulation and C receptors are sensitive to heterologous regulation by Ag II.     

Effects of calcium-antagonists on norepinephrine release from sympathetic nerve endings in rat mesenteric vasculature

The present study was designed to investigate whether Ca-antagonists influence norepinephrine release from the sympathetic nerve endings in resistance vessels. Isolated mesenteric vascular preparations of rats, perfused with Ringer-Locke solution, were used to determine the effects of verapamil or diltiazem on norepinephrine release from sympathetic nerve terminals. Pressor responses to exogenous norepinephrine and electrical nerve stimulation were recorded, and the norepinephrine contents of the perfusate were measured before and after the electrical nerve stimulation, using high pressure liquid chromatography with an electrochemical detector. Pressor responses to exogenous norepinephrine and electrical nerve stimulation were depressed dose-dependently by verapamil and diltiazem. The inhibition of the pressor responses for nerve stimulation was greater than exogenous norepinephrine. Both verapamil and diltiazem reduced norepinephrine release from the mesenteric arterial beds after the electrical nerve stimulation. These results indicate that Ca++-antagonists, such as verapamil and diltiazem, have inhibitory effects on norepinephrine release from the sympathetic nerve endings, in addition to their direct actions on the vascular smooth muscle. It is also suggested that the presynaptic inhibitory action of Ca++-antagonists could be due to the blockade of Ca++-channels in nerve cell terminals, which may be important in the clinical use of Ca-antagonists.