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PubMed1991

Evidence against serotonin-induced endothelium-dependent relaxation in bovine coronary artery.

Bovine coronary artery rings were mounted in tissue baths for the measurement of isometric contraction in order to test for serotonin-induced endothelium-dependent relaxation. A23187 caused a concentration-dependent relaxation in precontracted artery rings when the endothelium was intact, but not when it was removed. Endothelium removal had no effect on serotonin concentration contractile response curves (CRC) in normal Krebs' solution, but enhanced the response to serotonin in artery rings precontracted with 25 mM K+ Krebs' solution. In endothelium-intact, precontracted artery rings, ketanserin shifted the serotonin CRC to the right, but did not convert the contraction to relaxation. 5-Carboxamidotryptamine caused a weak contraction that was blocked by ketanserin, but not converted to relaxation. Inactivation of monoamine oxidase enhanced the contractile response to serotonin in precontracted artery rings in a manner identical to that caused by endothelium removal. Inactivation of monoamine oxidase had no effect in endothelium-denuded artery rings. De-endothelialized rabbit aorta strips pretreated with phenoxybenzamine were placed in close apposition to endothelium-intact coronary artery strips. Superoxide dismutase, acetylcholine and A23187 caused the precontracted rabbit aorta strip to relax, whereas serotonin had no effect. These results support the conclusion that the endothelium of the bovine coronary artery releases a relaxing factor both spontaneously and in response to acetylcholine and A23187. Serotonin appears to be incapable of releasing endothelium-derived relaxing factor or causing an endothelium-dependent relaxation. However, bovine coronary artery endothelium appears to be able to take up and metabolize serotonin.

Animals↗
PubMed1991

Pertussis toxin reduces endothelium-dependent and independent responses to alpha-2- adrenergic stimulation in systemic canine arteries and veins.

A pertussis toxin-sensitive guanine nucleotide regulatory protein (G-protein) is involved in the signal transduction of certain endothelium-dependent responses in mammalian arteries. To determine whether a similar mechanism mediates endothelium-dependent responses in mammalian veins, rings of canine femoral arteries and veins with and without endothelium were suspended for the measurement of isometric force in organ chambers. In femoral arteries, incubation of the rings with pertussis toxin (from Bordetella pertussis, 100 ng/ml for 2 hr) in the presence of indomethacin and propranolol did not reduce significantly endothelium-dependent relaxations to acetylcholine and adenosine diphosphate, thrombin or the calcium ionophore A23187. However, endothelium-dependent relaxations evoked by the alpha-2 adrenergic agonist UK 14,304 were blocked by the pertussis toxin. In venous rings, endothelium-dependent relaxations to acetylcholine were reduced by the toxin, whereas the endothelium-dependent relaxations evoked by adenosine diphosphate, thrombin and A23187 were not affected. UK 14,304 contracted the veins; these contractions were augmented by removal of the endothelium. Pertussis toxin inhibited contractions to UK 14,304 in venous rings without but not with endothelium. Relaxations of arterial and venous smooth muscle to nitric oxide were unaffected by the toxin. Contractions to phenylephrine were not altered by either removal of the endothelium or the toxin in the arteries or veins. These results suggest that the release of endothelium-derived relaxing factor in response to stimulation of purine and thrombin receptors probably does not involve a pertussis toxin-sensitive G-protein in canine femoral arteries or veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Role of endothelium in responses of isolated hepatic vessels to vasoactive agents.

The role of the endothelium as a participant in the responses to vasoactive agents was evaluated in isolated canine hepatic artery (HA) and portal vein (PV) rings. Endothelial and smooth muscle integrity was determined by pharmacologic responses as well as by histologic examination. Smooth muscle relaxation was expressed as the percent of decrease of norepinephrine-induced isometric contraction. Acetylcholine (ACh)-induced relaxation of the HA was abolished by removing the endothelium or by the addition of either hemoglobin, methylene blue (MB) or Ng-mono-methyl-L-arginine. In addition, relaxation induced by nitroglycerin, but not that induced by prostaglandin E1, was attenuated by MB. These data suggest endothelium-dependency of the relaxation to ACh and mediation of the response by endothelium-derived relaxing factor through activation of guanylate cyclase. In contrast, ACh produced contraction of the PV which was unaffected by removing the endothelium. The calcium ionophore, A23187, on the other hand, produced relaxation of the PV, which was significantly decreased by removing the endothelium. Relaxation of both HA and PV, produced by 2-chloroadenosine (2-C-Ado) was partially attenuated by removing the endothelium. With the endothelium intact, neither hemoglobin, MB, Ng-monomethyl-L-arginine nor indomethacin affected the responses to 2-C-Ado in the HA and PV, suggesting that the responses were not mediated by endothelium-derived relaxing factor or products of guanylate cyclase or cyclooxygenase activity. Nitroglycerin relaxed both vessels in the presence or absence of endothelium, indicating that removal of the endothelium had not affected smooth muscle function.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Chloroadenosine↗
PubMedDate not supplied

Decreased modulation by endothelium of noradrenaline-induced contractions in aorta from stroke-prone spontaneously hypertensive rats.

Influences of endothelium on contractions of aortic ring preparations from 15 to 17 weeks old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto rats (WKY) were compared. Noradrenaline-induced contraction was potentiated by endothelium removal; the potentiation was greater in the WKY aorta. Noradrenaline (10(-5) M) induced a biphasic contraction in endothelium-intact WKY aorta, while endothelium-intact SHRSP aorta or endothelium-removed preparations of both strains showed a monophasic sustained contraction. The tension changes in high-K-induced contracture of the endothelium-intact preparation was less pronounced in both WKY and SHRSP aortae. The relaxation by acetylcholine (10(-5) M) of endothelium-intact aortae, precontracted with noradrenaline (5 X 10(-7) M), amounted to 78% in the WKY and to 44% in the SHRSP preparation. In endothelium-removed aortae, sodium nitroprusside induced a comparable relaxation in both WKY and SHRSP preparations. These results indicate that the endothelium plays an important role in controlling the noradrenaline-induced contraction and that the lower influence of endothelium in the SHRSP aorta is most likely due to a decreased activity of this endothelium.

Acetylcholine↗
PubMed1988

Influence of the endothelium on tone and the response of isolated pig coronary artery to norepinephrine.

The influence of the endothelium on smooth muscle tone and the response of the pig right coronary artery to norepinephrine (NE) was studied. Isolated rings of artery with and without endothelium were stretched in the presence of nitroprusside to a tension previously determined to be optimal for contraction. During wash out of the nitroprusside, rings without endothelium spontaneously generated tone representing 24% of the contraction caused by potassium (120 mM); in rings with endothelium no significant spontaneous tone was observed. Relaxations were caused by NE in rings with endothelium contracted with prostaglandin F2 alpha (PGF2 alpha). In rings without endothelium, NE relaxed spontaneously generated tone as well as that produced by PGF2 alpha. Independent of the mode or degree of contraction, rings with endothelium were more sensitive to NE than rings without endothelium. The difference in sensitivity to NE between rings with and without endothelium was likely due to endothelial cell alpha-2 adrenoceptors, inasmuch as the difference was abolished by rauwolscine. In the presence of propranolol and prazosin, endothelium-dependent relaxations were observed which were also inhibited by rauwolscine. Nevertheless, beta adrenoceptors are the predominant mediator of the relaxation to NE of pig coronary smooth muscle, because propranolol caused a greater shift to the right of the relaxation induced by NE compared to that caused by endothelium removal. Accordingly, under resting conditions, NE caused contractions only in the presence of propranolol. These contractions were attenuated by prazosin or rauwolscine, but blocked only by a combination of both alpha adrenoceptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor.

Removal of endothelial cells on rings of rat aorta increased the sensitivity to the selective alpha-1 adrenoceptor agonist phenylephrine, to the nonselective alpha adrenoceptor agonist norepinephrine and to the selective alpha-2 adrenoceptor agonist clonidine. In the case of the first two, which are strong agonists for the alpha-1 adrenoceptor-mediating contraction, removal of endothelium increased sensitivity 4- and 6-fold at the EC30 level, but produced little or no increase in maximum. In the case of clonidine, a partial agonist for the alpha-1 adrenoceptor, which gave only about 15% of the maximum given by phenylephrine on endothelium-containing rings, removal of the endothelium not only shifted the curve to the left but also increased the maximum to about 50% of that given by phenylephrine. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium-derived relaxing factor (EDRF), as hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent depression was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in precontracted rings even when its contractile action was blocked by the alpha-1 adrenoceptor antagonist prazosin. Further evidence against alpha adrenoceptor agents stimulating release of EDRF was that neither phenylephrine nor clonidine induced a rise in cyclic GMP in aortic rings, whereas acetylcholine, which does release EDRF, caused a large rise in cyclic GMP content. The possibility that the muscle cells of intact rat aortic rings were under the tonic influence of released EDRF was supported by the finding that, in the absence of any contractile agent, hemoglobin induced a fall in the basal level of cyclic GMP in endothelium-containing rings. Also consistent with EDRF being released spontaneously was the finding that contraction induced by 5-hydroxytryptamine, like that by alpha-adrenergic agonists, was also depressed in endothelium-containing rings of aorta. When the efficacy of phenylephrine as an alpha-1 agonist was reduced to about the initial efficacy of clonidine by irreversible inactivation of a very large fraction of alpha-1 adrenoceptors of the smooth muscle cells by pretreatment with dibenamine, the concentration-contraction curves for phenylephrine for both endothelium-containing rings and for endothelium-denuded rings now became very similar to the corresponding curves obtained for clonidine before receptor inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1994

The endothelium and vascular effects of the ACE inhibitor trandolaprilat.

Experiments were designed to study the effects of trandolaprilat on endothelium-dependent responses in isolated blood vessels. Rings of either femoral or left circumflex coronary arteries of the dog or thoracic aortas of normotensive rats were suspended in organ chambers for isometric tension recording. During contractions induced by prostaglandin F2 alpha, trandolaprilat did not cause direct endothelium-dependent or -independent relaxation. However, when given to preparations incubated with angiotensin I or bradykinin, the compound evoked significant endothelium-dependent relaxation. By contrast, trandolaprilat failed to cause any change in tension when given in the presence of acetylcholine (ACh). In rings of femoral arteries, trandolaprilat potentiated the endothelium-dependent relaxation evoked by bradykinin and adenosine diphosphate; it did not modify the endothelium-dependent relaxations induced by ACh, substance P, or thrombin. In rings of femoral arteries without endothelium, trandolaprilat augmented relaxation induced by adenosine diphosphate (ADP) but not by adenosine. In perfused coronary arteries with but not those without endothelium, trandolaprilat caused relaxation in the absence of exogenous bradykinin (or ADP). These experiments suggest that trandolaprilat does not directly release endothelium-derived relaxing factor from the endothelial cells, does not interfere with the ability of the endothelium to release endothelium-derived relaxing factor, augments the endothelium-dependent responses to bradykinin (given exogenously or produced locally) and angiotensin I by direct interaction with converting enzyme, and potentiates the relaxation induced by ADP by augmenting its direct effect on vascular smooth muscle.

Adenosine Diphosphate↗
PubMed1994

Endothelium and the regulation of vascular tone with emphasis on the role of nitric oxide. Physiology, pathophysiology and clinical implications.

After the discovery by Furchgott and colleagues in 1980 that the endothelium plays an obligatory role in acetylcholine-induced vasodilation many investigators have elucidated the role of the endothelium in the regulation of vascular tone. While the sympathetic nervous system serves the organism as a whole, the endothelium appears to act as a local regulator adapting blood flow to local metabolic needs. A variety of endothelium-derived relaxing and contracting factors such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, endothelin and thromboxane A2 play a role in the endothelium-dependent control of vascular tone. Furthermore, nitric oxide inhibits thrombocyte aggregation and adhesion. Many diseases have been reported to be associated with an impaired endothelium-dependent vasodilation which may contribute to an increased susceptibility to vasospasm, decreased inhibition of thrombus formation and an impaired ability to reduce vascular resistance in ischaemic conditions. In hypertension, hypercholesterolaemia and diabetes mellitus this impairment may be interpreted as an early marker of a process that ultimately will lead to atherosclerosis. The impaired endothelium-dependent vasodilation probably contributes to the increased peripheral vascular resistance in hypertension and heart failure. The role of the endothelium does not seem to be restricted to cardiovascular diseases. Several mediators of inflammation stimulate the endothelium to release nitric oxide, suggesting an important role of the endothelium in the haemodynamic sequelae of sepsis.

Cardiovascular Diseases↗
PubMed1995

Evidence for endothelium-derived relaxing factor/nitric oxide in equine digital arteries.

OBJECTIVE: To test the hypothesis that endothelium-derived nitric oxide modulates vasomotor reactivity in equine digital arteries. DESIGN: Digital arteries were isolated from adult horses, and their vasodilator properties were examined in an in vitro controlled environment. ANIMALS: Five adult horses (1 gelding, 4 mares) without evidence of hoof or vascular disease were studied. PROCEDURE: Arterial rings with or without endothelium were exposed to endothelium-dependent vasodilator drugs in the presence or absence of a pharmacologic inhibitor of the enzyme nitric oxide synthase. RESULTS: Vasodilator effects of 3 endothelium-dependent vasorelaxant agents were significantly greater in endothelium-intact vessels than in endothelium-denuded vessels. Moreover, a nitric oxide synthase inhibitor reduced vasodilator responses to endothelium-dependent vasodilators in endothelium-intact arteries, but had no discernable effects in endothelium-denuded arteries. CONCLUSIONS: These findings indicate the presence of endothelium-derived relaxing factor/nitric oxide in blood vessels of horses, and identify vascular endothelium as an endogenous modulator of vasomotor tone in the digital arteries of this species.

Acetylcholine↗
PubMed1995

Endothelium-derived relaxing factor is important in mediating the high output state in chronic severe anemia.

OBJECTIVES: We evaluated the endothelial and vascular smooth muscle function in patients with chronic severe anemia to determine whether increased basal nitric oxide levels contribute to the systemic vasodilation and high cardiac output seen in these patients. BACKGROUND: Patients with chronic severe anemia have a high output state due to a low systemic vascular resistance. However, the cause of the low vascular resistance is unclear. Because hemoglobin is a potent inhibitor of endothelium-derived relaxing factor, we postulated that in chronic severe anemia, low circulating hemoglobin results in reduced inhibition of endothelium-derived relaxing factor. The basal endothelium-derived relaxing factor activity therefore increases, and this contributes significantly to the low systemic vascular resistance and the hyperdynamic state seen in this condition. METHODS: Hemodynamic variables and forearm blood flow (using plethysmography) were measured in eight patients with chronic severe anemia before (hematocrit 16 +/- 2% [mean +/- SD]) and within 24 h of red blood cell transfusion (n = 6, hematocrit 30 +/- 1%) and in six control subjects. The effect on baseline blood flow of blocking endothelium-derived relaxing factor activity with NG-monomethyl-L-arginine was investigated. In addition, the effects of both endothelium-dependent and endothelium-independent vasodilators on forearm blood flow were tested. RESULTS: Baseline forearm blood flow was markedly increased in untreated patients (6.5 +/- 1.2 ml/min per 100 ml) compared with that in control subjects (2.8 +/- 0.7 ml/min per 100 ml, p < 0.0001, 95% confidence interval [CI] for difference -5 to -2.5). Red blood cell transfusion significantly reduced blood flow in the anemic patients to 3.5 +/- 1.1 ml/min per 100 ml (p < 0.001, 95% CI for difference -4.9 to -1.9), which was not significantly different from that in control subjects; increased systemic vascular resistance (796 +/- 141 to 1,230 +/- 151 dynes.s.cm-5, p < 0.001); and decreased cardiac output (4.9 +/- 0.6 to 3.5 +/- 0.5 liters/min per m2, p < 0.001). NG-monomethyl-L-arginine (16 mumol/min), a specific inhibitor of endothelium-derived relaxing factor, reduced forearm blood flow by an equal amount (p = 0.9, 95% CI for difference -0.7 to 0.8) in control subjects (0.98 +/- 0.39 ml/min) and treated patients (1.03 +/- 0.8 ml/min) but caused a threefold greater decrease in flow (2.9 +/- 0.9 ml/min) in untreated patients (p = 0.0003, 95% CI for difference between untreated patients and control subjects 1.1 to 2.7). These findings suggest increased basal endothelium-derived relaxing factor activity in patients with anemia. Stimulated forearm blood flows (both endothelium dependent and endothelium independent) were similar in all groups, confirming normal endothelial and smooth-muscle function. CONCLUSIONS: These findings support the hypothesis that enhanced basal endothelium-derived relaxing factor activity makes an important contribution to the low systemic vascular resistance in chronic severe anemia.

Adult↗
PubMed1997

Impaired endothelium-dependent relaxation of human hepatic arteries after preservation with the University of Wisconsin solution.

OBJECTIVE: To evaluate the effect of University of Wisconsin solution on endothelium-dependent relaxation and contraction of human hepatic arteries in vitro. DESIGN: Human hepatic arteries were harvested from 24 patients with hepatocellular carcinoma who had undergone hepatectomy. SETTING: A tertiary care center. INTERVENTIONS: Human hepatic arteries (n = 6 in each group) were harvested during resection for hepatocellular carcinoma. The arteries in group 1 (i.e., the control group) were immediately studied without preservation. The arteries in group 2 were preserved in cold (4 degrees C) physiological solution for 1 hour, while the arteries in groups 3 and 4 were preserved in University of Wisconsin solution for 1 and 16 hours, respectively. Segments of control and preserved hepatic arteries with or without endothelium were then suspended in organ chambers to measure the isometric force. RESULTS: The relaxation of segments of the hepatic arteries with endothelium in response to acetylcholine and adenosine diphosphate was significantly (P < .05) greater than that of segments without endothelium. The maximal relaxation of hepatic arterial segments with endothelium in groups 3 and 4 in response to acetylcholine was notably different from that of segments in groups 1 and 2. The maximal relaxation of hepatic arterial segments with endothelium in groups 3 and 4 in response to adenosine diphosphate was notably different from that of segments in groups 1 and 2. Perfusate hypoxia (mean +/- SD PO2, 30 +/- 5 mm Hg) caused the endothelium-dependent contraction of the arteries (the median initial tension in groups 1, 2, 3, and 4 was 251%, 233%, 276%, and 260%, respectively; P > .05). CONCLUSIONS: The endothelium-dependent relaxation of human hepatic arteries in response to acetylcholine and adenosine diphosphate was notably attenuated by University of Wisconsin solution. The impaired endothelium-dependent relaxation by University of Wisconsin solution and the prominent endothelium-dependent contraction of human hepatic arteries would favor vasospasm and thrombosis after hepatic transplantation.

Adenosine↗
PubMed1991

Elevated guanosine 3':5'-cyclic monophosphate mediates the depression of nitrovasodilator reactivity in endothelium-intact blood vessels.

The influence of endothelium-derived nitric oxide (EDNO) on relaxation induced by the nitrovasodilators, sodium nitroprusside and sodium nitrite was assessed in phenylephrine-stimulated hamster thoracic aortas, a preparation that displays significant basal release of EDNO. Removal of the endothelium or treatment with the NO synthase inhibitors, NG-nitro-L-arginine (L-NAG, 10-30 microM) or NG-methyl-L-arginine (L-NMMA; 100 microM) increased the potency and, except for sodium nitroprusside in endothelium-denuded segments, also increased the efficacy of the nitrovasodilators. Removal of the endothelium had no effect on relaxations induced by isoproterenol, an indication that these effects were specific for the nitrovasodilators. Removal of the endothelium, treatment of endothelium-intact preparations with L-NAG or L-NMMA, or exposure of these vessels to the guanylate cyclase inhibitor, methylene blue (10 microM) increased reactivity of the aortas to the guanosine 3':5'-cyclic monophosphate (cGMP) analogue, 8-Br cGMP. Measurement of cGMP revealed that endothelium-intact segments had a 6.5 fold higher level of cGMP than endothelium-denuded preparations and that sodium nitroprusside increased cGMP in both preparations by similar amounts in a concentration-dependent fashion. Exposure of endothelium-denuded or L-NAG-treated segments to sodium nitroprusside, to mimic the effects of basally released EDNO, depressed sodium nitrite and 8-Br cGMP reactivity in a manner similar to endothelium-intact segments. These data indicate that EDNO increases cGMP levels in vascular smooth muscle and that the elevated cGMP levels depress nitrovasodilator and 8-Br cGMP reactivities.

Animals↗
PubMed1986

Effect of endothelium on basal and alpha-adrenoceptor stimulated calcium fluxes in rat aorta.

The rate of unstimulated influx of Ca2+ into rat aorta smooth muscle, measured as uptake of 45Ca, was inhibited in the presence of endothelium as compared to influx in the absence of endothelium. Efflux of 45Ca from unstimulated prelabelled tissues was also reduced in the presence of endothelium. In normal physiological solution the rate of influx and efflux of Ca2+ stimulated by B-HT 920 (1 and 10 microM), but not that stimulated by phenylephrine (30 nM and 1 microM), was also reduced in the presence of endothelium. In the presence of the calcium entry blocker flunarizine (3 microM), phenylephrine (1 microM) stimulated efflux of Ca2+ was inhibited by the presence of endothelium. A correlation between inhibition of Ca2+ influx and modulation of alpha-adrenoceptor agonist-induced contractions by endothelium could not be demonstrated, and methylene blue, an antagonist of endothelium mediated inhibition of B-HT 920 contractions, did not affect Ca2+ influx stimulated by the agonist. The effects of endothelium on Ca2+ influx and efflux are unlikely to be due to alterations by endothelium of diffusion of 45Ca or the agonists in the vessel. The results demonstrate that an endothelial derived factor or factors can reduce calcium influx into smooth muscle cells and also modulate the release of calcium from cells, perhaps by affecting intracellular calcium pumping mechanisms. A reduction of calcium influx cannot be the sole explanation for the modulatory effect of endothelium on alpha-adrenoceptor agonist-induced contractions but an effect on intracellular calcium metabolism may be important.

Animals↗
PubMed1990

Endothelium-derived vasoactive factors and regulation of vascular tone in human blood vessels.

The endothelium releases a variety of factors which can affect vascular tone. Endothelium-derived relaxing factor or nitric oxide is a very potent vasodilator and inhibitor of platelet function. Its release has been demonstrated in a variety of human blood vessels. In most human vascular preparations, prostacyclin does not significantly contribute to the endothelium-dependent relaxations. Prostacyclin is, however, an endothelium-derived product which can evoke vasodilation and inhibition of platelet aggregation. In addition, the endothelium of human veins can release endothelium-derived contracting factors produced by the cyclooxygenase pathway. Endothelin is an endothelium-derived vasoactive peptide which has profound vasoconstrictor properties in human arteries and particularly in veins. Its action can only be partially inhibited by calcium antagonists, while endothelium-derived nitric oxide and exogenous nitrovasodilators are effective antagonists of the peptide. The mechanisms and amounts of endothelin released in human blood vessels remains to be defined. Under physiological conditions, endothelium-derived relaxing factors appear to dominate. The release of endothelium-derived nitric oxide is reduced in atherosclerotic human arteries. This indicates that in cardiovascular disease endothelial dysfunction occurs; this may contribute in the pathogenesis of coronary artery disease, pulmonary hypertension and stroke.

Animals↗
PubMed1987

Changes in vascular endothelium and its function in systemic arterial hypertension.

The various functions of arterial endothelium may be altered during pulmonary and arterial hypertension. Changes in the endothelium (or function) associated with hypertension are described. In both acute and chronic hypertension, permeability of the endothelium is enhanced. During the acute phase of hypertension, hyperplasia (cell replication) of the endothelium occurs while cell hypertrophy (enlarged cell size) and an increase in homocellular tight junctions are associated with sustained elevations of blood pressure. Endothelium may contribute to the increase in smooth muscle mass or cell number reported with various models of hypertension. Increased endothelial uptake or metabolism of norepinephrine and serotonin occurs during hypertension. The biotransformation of adenine nucleotides and various peptides by the endothelium is not altered by hypertension. Synthesis of prostacyclin is enhanced in the spontaneously hypertensive and Goldblatt hypertensive rat. Metabolism of prostaglandin E2, prostaglandin F2 alpha and prostacyclin by prostaglandin 15-hydroxydehydrogenase is impaired in the genetic models. Responses to endothelium-dependent vasodilators are impaired in acute and chronic models of hypertension. Production of relaxing factor by the endothelium is not inhibited, but rather the vascular smooth muscle fails to respond. Acute, severe hypertension potentiates the response to serotonin, presumably by attenuating the release or response to relaxing factor(s). In the aorta of the spontaneously hypertensive rat, the endothelium releases a constricting factor in response to acetylcholine. Pulmonary arterial endothelium (and other vessels) releases a vasoconstrictor that is blocked by inhibitors of cyclooxygenase. It is not clear whether this pressor factor is thromboxane A2. Cultured endothelial cells release a polypeptide that contracts arteries; however, any relation to hypertension is not known.

Acute Disease↗
PubMed1985

Purine-mediated relaxation and constriction of isolated rabbit mesenteric artery are not endothelium-dependent.

The distribution of P1- and P2-purinoceptors in isolated transverse ring preparations of rabbit mesenteric artery was studied by comparing responses to ATP, alpha, beta-methylene ATP and adenosine in the presence and absence of endothelium. At resting tone in the presence of endothelium, ATP, alpha, beta-methylene ATP and acetylcholine, but not adenosine, produced transient concentration-dependent contractions. Alpha, beta-Methylene ATP was 5000 times more potent than ATP in this respect. Contractions to ATP or alpha, beta-methylene ATP in intact preparations were not significantly different from preparations without endothelium, but contractions to acetylcholine were significantly enhanced in the absence of endothelium. In the presence of endothelium, after desensitisation of the preparations to alpha, beta-methylene ATP, contractions to ATP, but not those to noradrenaline, were either greatly reduced or abolished. In preparations with tone raised by noradrenaline, acetylcholine, ATP and adenosine each produced relaxation in the presence of endothelium; however, in the absence of the endothelium, relaxations to acetylcholine were abolished, while those to ATP and adenosine were not significantly altered. 8-Phenyltheophylline significantly antagonised relaxation to adenosine in the presence of endothelium, whereas relaxation to ATP was unaffected. In raised tone preparations, with and without endothelium, alpha, beta-methylene ATP caused further contraction. However, in raised tone preparations with or without endothelium, that had been desensitised to alpha, beta-methylene ATP before elevation of muscle tone, ATP still caused relaxation, whereas alpha, beta-methylene ATP had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Influence of the endothelium on the amplification by serotonin of vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation in rabbit isolated ear artery.

The influence of the vascular endothelium on the amplifying effect of serotonin on steady-state responses to noradrenaline (NA) and sympathetic nerve stimulation (SNS) has been studied in the rabbit isolated ear artery. Removal of the endothelium abolished the dilator effect of acetylcholine (ACh, 1 microM) obtained in the presence of NA (0.3 microM). Responses to NA were increased after endothelium removal; however, responses to SNS were unaffected. Serotonin in a concentration which did not itself produce vasoconstriction (100 nM) increased responses of endothelium-intact preparations to NA and SNS and of endothelium-denuded preparations to SNS but had no effect on NA responses of endothelium-denuded preparations. If neuronal uptake was inhibited with cocaine (1 microM), serotonin markedly amplified responses to NA and SNS in both endothelium-intact and endothelium-denuded preparations. These results suggest that the endothelium influences the amplifying effect of serotonin on responses of rabbit ear artery to NA but not to SNS. Inhibition of removal of serotonin and NA by neuronal uptake may extend the facilitatory interaction between NA and serotonin to smooth muscle cells which are not subject to the inhibitory influence of an endothelium derived relaxing factor.

Animals↗
PubMed1994

Evidence that histamine is involved as a mediator of endothelium-dependent contraction induced by A23187 in bovine intrapulmonary vein.

This study was initiated to test the hypothesis that histamine can act as an endothelium-derived contracting factor in bovine isolated intrapulmonary vein. The effects of calcium ionophore, calcimycin (A23187), on isometric tension were compared in unstimulated rings of intrapulmonary vein with and without endothelium. A23187 (0.1-10 microM) induced concentration-related contraction when endothelium was present. Destruction of endothelium markedly inhibited A23187-induced contraction. Methylene blue, hemoglobin or NG-methyl-L-arginine significantly enhanced A23187-induced contraction only in venous rings with endothelium consistent with attenuation of the contraction by the concomitant release of endothelium-derived relaxing factor (nitric oxide) [EDRF(NO)]. Histamine H1 receptor antagonists inhibited, and iproniazid enhanced, contraction elicited by A23187. A23187 induced release of greater amounts of histamine from venous rings with than without endothelium. A23187-induced contraction was not mimicked by the mast cell activator, compound 48/80, and was not inhibited by preexposure to compound 48/80 or in the presence of cromolyn or doxantrazole. A23187-induced contraction was not inhibited by pretreatment with indomethacin, phentolamine, lipoxygenase inhibitors or superoxide dismutase. The results indicate that A23187 induces endothelium-dependent contraction in bovine intrapulmonary vein and support histamine as one major mediator involved. The association of destruction of endothelium with an inhibition of both A23187-induced contraction and histamine release is consistent with the endothelium as a source for histamine which can exert a local vasoconstrictor effect in bovine intrapulmonary vein.

Animals↗