Endothelin-1 and -3 cause endothelium-dependent hyperpolarization in the rat mesenteric artery

1993 ◽  
Vol 265 (6) ◽  
pp. H2137-H2141 ◽  
Author(s):  
M. Nakashima ◽  
P. M. Vanhoutte
Keyword(s):  
Mesenteric Artery ◽  
Mesenteric Arteries ◽  
Receptor Subtype ◽  
Spontaneously Hypertensive ◽  
Rat Mesenteric Artery ◽  
Significant Difference ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Wistar Kyoto ◽  
Eta Receptor Antagonist

The present study was designed to determine whether endothelin (ET) induces endothelium-dependent hyperpolarization in the isolated rat mesenteric artery and, if so, to identify the receptor subtype involved. Main superior mesenteric arteries of Wistar-Kyoto and spontaneously hypertensive rats were used for the measurement of electrical responses of smooth muscle cells, using glass microelectrode. In tissues with endothelium of both strains, ET-1 (10(-8) M) caused an initial transient hyperpolarization followed by a sustained depolarization. In tissues without endothelium, only depolarization was observed. ET-3 (10(-8) M) produced transient hyperpolarizations only in preparations with endothelium. There was no significant difference in maximal amplitude of hyperpolarization between the two strains. BQ-123 (selective ETA-receptor antagonist) blocked the depolarization to ET-1 but did not inhibit hyperpolarizing responses to either isopeptide. IRL-1620 (specific ETB-receptor agonist) produced transient membrane hyperpolarizations in tissues with endothelium. The hyperpolarizations induced by ET were not affected by NG-nitro-L-arginine. These data suggest that both ET-1 and ET-3 can cause endothelium-dependent hyperpolarization in the rat mesenteric artery and that the endothelial receptor involved may belong to ETB subtype.

Effect of diabetes on vascular smooth muscle function in normotensive and spontaneously hypertensive rat mesenteric artery

1987 ◽  
Vol 65 (11) ◽  
pp. 2274-2280 ◽  
Author(s):  
D. K. Agrawal ◽  
J. H. McNeill
Keyword(s):  
Mesenteric Artery ◽  
Spontaneously Hypertensive Rat ◽  
Functional Responses ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Rat Mesenteric Artery ◽  
Significant Difference ◽  
Adrenoceptor Agonists ◽  
Wistar Kyoto ◽  
The Right

We have examined the functional responses to α-adrenoceptor agonists (α1-selective: methoxamirte and phenylephrine; α2-selective: clonidine and B-HT 920; non-selective: norepinephrine, serotonin and K+ in ring segments of mesenteric artery of control and streptozotocin-induced diabetic spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Systolic blood pressure and contractile responses were examined after 12 weeks of diabetes. There was no significant change in the diabetic WKY rats as compared with the control WKY rats. However, diabetic SHR had significantly less hypertension than control SHR. Responses to serotonin and α2-adrenoceptor agonists were augmented significantly in arteries from control SHR animals as compared with vessels from WKY animals. There was no significant difference in the force of contraction generated by other agonists in both nondiabetic groups. Responses to all agonists in WKY diabetic and to methoxamine and K+ in SHR diabetic arteries were increased as compared with their respective controls. ED50 values for each agonist were similar in all groups. Indomethacin (5 μM) shifted the dose–response curve to norepinephrine to the right in arteries from all groups of animals. However, in the diabetic SHR and WKY, there was a significant reduction in norepinephrine maximum response. Nifedipine was more potent in inhibiting the contraction to K+ and serotonin in WKY diabetic arteries as compared with WKY controls. However, nifedipine inhibited the responses to all agonists with equal potency in the control and diabetic SHR vessels. These results suggest the involvement of α2-adrenoceptors and serotonin receptors in the development and (or) the maintenance of hypertension. Furthermore, the hyperresponsiveness of the diabetic vessels could be due to an alteration in the postreceptor excitation–contraction coupling, possibly involving prostaglandin and an increased activity of calcium channels.

Age-related changes in endothelium-dependent hyperpolarization in the rat mesenteric artery

1993 ◽  
Vol 265 (2) ◽  
pp. H509-H516 ◽  
Author(s):  
K. Fujii ◽  
S. Ohmori ◽  
M. Tominaga ◽  
I. Abe ◽  
Y. Takata ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
K Channel ◽  
Aged Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Age Related ◽  
Rat Mesenteric Artery ◽  
Wistar Kyoto ◽  
Age Related Changes

This study was designed to determine the age-related changes in the endothelium-dependent hyperpolarization to acetylcholine (ACh) and its contribution to relaxation in the isolated mesenteric artery from normotensive and hypertensive rats. Membrane potentials and contractions were recorded in arteries from male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) that were 5-6 wk old (young), 6-8 mo old (adult), and 20-26 mo old (aged). Endothelium-dependent hyperpolarizations produced by ACh, applied both at the resting state of the membrane and under conditions of depolarization with norepinephrine (10(-5) M), were markedly impaired in aged WKY rats, adult SHR, and aged SHR. Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10(-5) M norepinephrine were also impaired in aged WKY rats, adult SHR, and aged SHR even in the presence of indomethacin. Furthermore, in these rats, N omega-nitro-L-arginine, an inhibitor of nitric oxide formation, showed potent inhibitory effects on the relaxations, whereas the 20 mM high K+ solution that reduces hyperpolarization had less pronounced effects. Hyperpolarizations and relaxations to cromakalim (10(-5) M), a K(+)-channel opener, were on the whole preserved in aged rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced with aging as well as by hypertension, and this would, in part, account for the impaired relaxation to ACh in arteries of both aged rats and hypertensive rats.

scholarly journals Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246254
Author(s):  
Lucía Isidoro-García ◽  
Diva M. Villalpando ◽  
Mercedes Ferrer
Keyword(s):  
Mesenteric Artery ◽  
Electrical Field Stimulation ◽  
Mesenteric Arteries ◽  
Hypertensive Rats ◽  
No Donor ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Vasomotor Function ◽  
Wistar Kyoto ◽  
And Function

Androgens may exert cardiovascular protective actions by regulating the release and function of different vascular factors. In addition, testosterone (TES) and its 5-reduced metabolites, 5α- and 5β-dihydrotestosterone (5α- and 5β-DHT) induce vasorelaxant and hypotensive effects. Furthermore, hypertension has been reported to alter the release and function of the neurotransmitters nitric oxide (NO), calcitonin gene-related peptide (CGRP) and noradrenaline (NA). Since the mesenteric arteries possess a dense perivascular innervation and significantly regulate total peripheral vascular resistance, the objective of this study was to analyze the effect of TES, 5α- and 5β-DHT on the neurogenic release and vasomotor function of NO, CGRP and NA. For this purpose, the superior mesenteric artery from male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to analyze: (i) the effect of androgens (10 nM, incubated for 30 min) on the neurogenic release of NO, CGRP and NA and (ii) the vasoconstrictor-response to NA and the vasodilator responses to the NO donor, sodium nitroprusside (SNP) and exogenous CGRP. The results showed that TES, 5α- or 5β-DHT did not modify the release of NO, CGRP or NA induced by electrical field stimulation (EFS) in the arteries of SHR; however, in the arteries of WKY rats androgens only caused an increase in EFS-induced NO release. Moreover, TES, and especially 5β-DHT, increased the vasodilator response induced by SNP and CGRP in the arteries of SHR. These findings could be contributing to the hypotensive/antihypertensive efficacy of 5β-DHT previously described in conscious SHR and WKY rats, pointing to 5β- DHT as a potential drug for the treatment of hypertension.

scholarly journals Autocrine effects of endothelin-1 on leukocyte-endothelial interaction: stimulation of endothelin B receptor subtype reduces endothelial adhesiveness via a nitric oxide-dependent mechanism

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 3894-3900 ◽  
Author(s):  
T Murohara ◽  
AM Lefer
Keyword(s):  
Nitric Oxide ◽  
Receptor Antagonist ◽  
Receptor Subtype ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Endothelin B ◽  
Eta Receptor Antagonist ◽  
Inhibition Of Thrombin

The effects of endothelin-1 (ET-1) on P-selectin-mediated leukocyte endothelial interaction were examined in vitro. Adherence of autologous polymorphonuclear leukocytes (PMNs) to the endothelium was markedly enhanced by endothelial stimulation with either (2 U/mL) thrombin, (1 mumol/L) histamine, or (100 nmol/L) phorbol myristate acetate (PMA). In contrast, ET-1 alone (10 and 100 nmol/L) only slightly increased the number of adhering PMNs. The increased PMN adherence to thrombin- or histamine-stimulated endothelium, which was blocked by an anti-P-selectin monoclonal antibody, was also significantly attenuated by preincubation of coronary segments with (100 nmol/L) ET-1. We further investigated the mechanism of this anti-adherence action of ET-1 on thrombin-stimulated endothelial adhesiveness. Preincubation of coronary segments with a selective ETA receptor antagonist, BQ485 (1 mumol/L), had no effect on ET-1 inhibition of thrombin-induced PMN adherence. In contrast, preincubation with a selective ETB receptor antagonist, BQ788 (1 mumol/L) significantly reversed ET-1 inhibition of thrombin-induced PMN adherence, whereas the selective ETB receptor agonist BQ-3020 mimicked the inhibitory action of ET-1 on thrombin-induced PMN adherence. Furthermore, (100 mumol/L) N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, significantly attenuated ET-1 inhibition of thrombin-stimulated PMN adherence. These results suggest that ET-1 may inhibit P-selectin-mediated leukocyte-endothelial interaction via ETB receptor stimulation and subsequent endothelial NO formation. This autocrine effect of ET-1 may be involved in pathophysiologic states such as early atherogenesis by preventing leukocyte-endothelial interaction in constricted blood vessels.

scholarly journals ETB2 receptor subtype stimulation relaxes the iris sphincter muscle

2009 ◽  
pp. 835-842
Author(s):  
A Rocha-Sousa ◽  
J Saraiva ◽  
M Amaral ◽  
P Alves-Faria ◽  
F Falcão-Reis ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Receptor Subtype ◽  
Sphincter Muscle ◽  
Receptor Stimulation ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Rabbit Iris Sphincter ◽  
Eta Receptor Antagonist ◽  
Rabbit Iris ◽  
Iris Sphincter

Effects of ETB receptor stimulation and its subcellular pathways were evaluated in carbachol pre-contracted rabbit iris sphincter muscles (n=51). ETB stimulation with sarafotoxin (SRTX-c; 10-10-10-6 M) was tested in the absence (n=7) or presence of 10-5 M of: BQ-788 (ETB2 receptor antagonist; n=6), L-NA (NOS inhibitor; n=7) or indomethacin (cyclooxygenase inhibitor; n=10). Effects of ETB stimulation by endothelin-1 (ET-1; 10-10– 10-7 M) in the presence of an ETA receptor antagonist (BQ-123; 10-5 M; n=7) and of ETB1 stimulation by IRL-1620 (10-10–10-7 M; n=7) were also tested. Finally, the effects of SRTX-c (10-9–10-7 M) in electric field stimulation (EFS) contraction were evaluated (n=7). ETB receptor stimulation by SRTX-c or ET-1 in presence of BQ-123 promoted a concentration-dependent relaxation of the rabbit iris sphincter muscle by 10.8±2.0 % and 9.4±1.8 %, respectively. This effect was blocked by BQ-788 (-2.3±2.0 %), L-NA (4.5±2.3 %) or indomethacin (2.3±2.9 %). Selective ETB1 stimulation by IRL-1620 did not relax the iris sphincter muscle (0.9±5.4 %). EFS elicited contraction was not altered by SRTX-c. In conclusion, ETB receptor stimulation relaxes the carbachol precontracted iris sphincter muscle, an effect that is mediated by the ETB2 receptor subtype, through NO and the release of prostaglandins.

scholarly journals Effect of Endothelin-1 on Corticosteroid Secretion by the Frog Adrenal Gland Is Mediated by an EndothelinA Receptor*

Endocrinology ◽  
1997 ◽  
Vol 138 (10) ◽  
pp. 4358-4363 ◽  
Author(s):  
Franck Cartier ◽  
Isabelle Remy-Jouet ◽  
Alain Fournier ◽  
Hubert Vaudry ◽  
Catherine Delarue
Keyword(s):  
Adrenal Gland ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Receptor Subtype ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Eta Receptor Antagonist ◽  
Corticosteroid Secretion

Abstract We have previously reported that endothelin-1 (ET-1) stimulates the in vitro secretion of corticosterone and aldosterone from the adrenal gland of the frog Rana ridibunda. The aim of the present study was to investigate the pharmacological profile of the endothelin receptor subtype involved in the corticotropic effect of ET-1. The mixed ETA/ETB receptor antagonist Ro 47–0203 (10−5m) totally blocked the stimulatory effect of ET-1 (5 × 10−9m) on corticosterone and aldosterone secretion. The action of ET-1 was also inhibited by the selective ETA receptor antagonist BQ-485 (10−7m). In contrast, the selective ETB receptor antagonist IRL 1038 (10−6m) did not affect the response of the frog adrenal gland to ET-1. In addition, the selective ETB receptor agonist IRL 1620 (10−6m) did not mimic the stimulatory effect of ET-1. The high affinity ETC receptor agonist endothelin-3 (ET-3) stimulated corticosteroid secretion, but was 400 times less potent than ET-1. Moreover, the action of ET-3 was also blocked by BQ-485 (10−7m). These data indicate that the stimulatory effects of ET-1 and ET-3 on corticosteroid secretion by the frog adrenal gland are mediated by an ETA receptor subtype.

Functional changes in adenylyl cyclases and associated decreases in relaxation responses in mesenteric arteries from diabetic rats

2005 ◽  
Vol 289 (5) ◽  
pp. H2234-H2243 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Kentaro Wakabayashi ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata
Keyword(s):  
Mesenteric Artery ◽  
Diabetic Rats ◽  
Functional Change ◽  
Water Soluble ◽  
Mesenteric Arteries ◽  
Diabetic Rat ◽  
Adenylyl Cyclases ◽  
Camp Production ◽  
Functional Changes ◽  
Rat Mesenteric Artery

To assess the functional change in adenylyl cyclases (AC) associated with the diabetic state, we investigated AC-mediated relaxations and cAMP production in mesenteric arteries from rats with streptozotocin (STZ)-induced diabetes. The relaxations induced by the water-soluble forskolin (FSK) analog NKH477, which is a putative AC5 activator, but not by the β-adrenoceptor agonist isoproterenol (Iso) and the AC activator FSK, were reduced in intact diabetic mesenteric artery. In diabetic rats, however, Iso-, FSK-, and NKH477-induced relaxations were attenuated in the presence of inhibitors of nitric oxide synthase and cyclooxygenase. To exclude the influence of phosphodiesterase (PDE), we also examined the relaxations induced by several AC activators in the presence of 3-isobutyl-1-methylxanthine (IBMX; a PDE inhibitor). Under these conditions, the relaxation induced by Iso was greatly impaired in STZ-diabetic rats. This Iso-induced relaxation was significantly attenuated by pretreatment with SQ-22536, an AC inhibitor, in mesenteric rings from age-matched controls but not in those from STZ-diabetic rats. Under the same conditions, the relaxations induced by FSK or NKH477 were impaired in STZ-diabetic rats. Neither FSK- nor A-23187 (a Ca2+ ionophore)-induced cAMP production was significantly different between diabetics and controls. However, cAMP production induced by Iso or NKH477 was significantly impaired in diabetic mesenteric arteries. Expression of mRNAs and proteins for AC5/6 was lower in diabetic mesenteric arteries than in controls. These results suggest that AC-mediated relaxation is impaired in the STZ-diabetic rat mesenteric artery, perhaps reflecting a reduction in AC5/6 activity.

scholarly journals Regulation of the Endothelin/Endothelin Receptor System by Interleukin-1β in Human Myometrial Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4878-4886 ◽  
Author(s):  
Michelle Breuiller-Fouché ◽  
Catherine Morinière ◽  
Emmanuelle Dallot ◽  
Stéphanie Oger ◽  
Régis Rebourcet ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
Mrna Levels ◽  
Receptor System ◽  
Myometrial Cell ◽  
Myometrial Cells ◽  
Uterine Contractions ◽  
Eta Receptor ◽  
Etb Receptor

Proinflammatory cytokines produced at the fetomaternal interface, such as IL-1β, have been implicated in preterm and term labor. The present study was performed to evaluate the influence of IL-1β on the endothelin (ET)/ET receptor system in human myometrial cells. We report that myometrial cells under basal conditions not only respond to but also secrete ET-1, one of the main regulators of uterine contractions. Prolonged exposure of the cells to IL-1β led to a decrease in prepro-ET-1 and ET-3 mRNA correlated with a decrease in immunoreactive ET-1 and ET-3 levels in the culture medium. Whereas ETA receptor expression at both protein and mRNA levels was not affected by IL-1β treatment, we demonstrated an unexpected predominance of the ETB receptor subtype under this inflammatory condition. Whereas the physiological function of ETB remains unclear, we confirmed that only ETA receptors mediate ET-1-induced myometrial cell contractions under basal conditions. By contrast, prolonged exposure of the cells to IL-1β abolished the contractile effect induced by ET-1. Such a regulation of IL-1β on the ET release and the balance of ETA to ETB receptors leading to a loss of ET-1-induced myometrial cell contractions suggest that complex regulatory mechanisms take place to constraint the onset of infection-induced premature contractions.

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