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 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.

Interaction among ET-1, endothelium-derived nitric oxide, and prostacyclin in pulmonary arteries and veins

1994 ◽  
Vol 267 (1) ◽  
pp. H139-H147 ◽  
Author(s):  
T. M. Zellers ◽  
J. McCormick ◽  
Y. Wu
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Potent Vasoconstrictor ◽  
Eta Receptor Antagonist ◽  
Arteries And Veins

Endothelin-1 causes vasodilation of the intact porcine pulmonary vascular bed. To determine the cause of this vasodilation, we investigated the interactions of endothelin-1 (ET-1), endothelium-derived nitric oxide (EDNO), and prostacyclin in isolated small porcine pulmonary arteries and veins under in vitro conditions. ET-1 caused concentration-dependent contractions in arteries and veins, augmented by the nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine, in pulmonary veins. BQ-123 (ETA-receptor antagonist) depressed the ET-1-induced contractions. Sarafotoxin S6C, an ETB-receptor agonist, caused contractions of pulmonary veins only. Endothelium-dependent relaxations to bradykinin and ET-1 were greater in pulmonary veins compared with arteries, inhibited by N omega-nitro-L-arginine, and reversed by L-arginine. BQ-123 augmented ET-1-induced arterial relaxation. ET-3 and sarafotoxin S6C, ETB-receptor agonists, caused comparable endothelium-dependent relaxations in arteries and veins. ET-1 caused a fourfold greater increase in prostacyclin release in pulmonary veins compared with arteries. We conclude that ET-1 is a potent vasoconstrictor of porcine pulmonary vessels and stimulates the release of EDNO and prostacyclin, which oppose the contractions to the peptide. The release of these endothelium-derived vasodilators appears greater in pulmonary veins.

Effects of 17 beta-estradiol on coronary microvascular responses to endothelin-1

1996 ◽  
Vol 271 (3) ◽  
pp. H1117-H1124 ◽  
Author(s):  
K. G. Lamping ◽  
D. W. Nuno
Keyword(s):  
Nitric Oxide ◽  
Left Ventricle ◽  
Receptor Antagonist ◽  
Male And Female ◽  
Small Arteries ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Eta Receptor Antagonist ◽  
Dose Dependent

The objective of this study was to examine the effects of 17 beta-estradiol on responses of coronary microvessels to endothelin-1 (ET-1). With the use of isolated pressurized coronary microvessels from the left ventricle of male or female dogs, constrictions to ET-1 were similar in vessels from male and female dogs. 17 beta-Estradiol (1 microM) attenuated constriction to ET-1 of small arteries from both male (percent constriction at 10 microM control: 39 +/- 9%, estradiol: 3 +/- 2%; P < 0.05) and female (percent constriction at 10 microM control: 39 +/- 8%, estradiol: 6 +/- 3%; P < 0.05) dogs similarly. In contrast, testosterone (1 microM) had no effect on constriction to ET-1. Constrictions to ET-1 were completely abolished by BQ-123 (1 microM), a selective ETA-receptor antagonist, and enhanced by BQ-788 (1 microM), a selective ETB-receptor antagonist. Constrictions to ET-1 alone were not altered by indomethacin (Indo, 10 microM) or NG-nitro-L-arginine (L-NNA, 100 microM). 17 beta-Estradiol produced dose-dependent relaxation of coronary microvessels preconstricted with ET-1 that was similar to the response to testosterone and progesterone. Indo or L-NNA alone had no effect on relaxation to 17 beta-estradiol. However, the combination of Indo and L-NNA attenuated Taxation to 17 beta-estradiol (percent dilation at 1 microM control: 64 +/- 13%; Indo plus L-NNA: 21 +/- 6%; P < 0.05) but did not affect relaxation to testosterone. Thus 17 beta-estradiol attenuated constrictions of coronary microvessels to ET-1 more than did similar concentrations of testosterone. The ability of 17 beta-estradiol to modulate responses to endothelin may involve release of vasodilator prostaglandins and/or nitric oxide by 17 beta-estradiol.

Analysis of vasocontractile responses to endothelin-1 in rabbit retinal vessels using an ETA receptor antagonist and an ETB receptor agonist

Life Sciences ◽  
1993 ◽  
Vol 53 (6) ◽  
pp. PL111-PL115 ◽  
Author(s):  
Kazuo Takei ◽  
Tsuyoshi Sato ◽  
Tomohito Nonoyama ◽  
Takashi Miyauchi ◽  
Katsutoshi Goto
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Retinal Vessels ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Eta Receptor Antagonist

In vitro and in vivo effects of endothelin-1 and YM598, a selective endothelin ETA receptor antagonist, on the lower urinary tract

2008 ◽  
Vol 580 (3) ◽  
pp. 394-400 ◽  
Author(s):  
Masashi Ukai ◽  
Hironori Yuyama ◽  
Akira Fujimori ◽  
Akiko Koakutsu ◽  
Masanao Sanagi ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Receptor Antagonist ◽  
Lower Urinary Tract ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Eta Receptor Antagonist ◽  
In Vivo Effects ◽  
Lower Urinary

Differential regulation of renal regional blood flow by endothelin-1

1996 ◽  
Vol 271 (6) ◽  
pp. F1166-F1172 ◽  
Author(s):  
K. Gurbanov ◽  
I. Rubinstein ◽  
A. Hoffman ◽  
Z. Abassi ◽  
O. S. Better ◽  
...  
Keyword(s):  
Blood Flow ◽  
Receptor Antagonist ◽  
Bolus Injection ◽  
Regional Blood Flow ◽  
Doppler Flowmetry ◽  
Endothelin 1 ◽  
Male Wistar Rats ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Eta Receptor Antagonist

The present study evaluated the effects and mechanisms of action of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively). CBF and MBF were measured simultaneously by laser-Doppler flowmetry in anesthetized male Wistar rats. Bolus injection of ET-1 (1.0 nmol/kg iv) produced a sustained decrease in CBF (delta = -30%) and a transient increase in MBF (delta = +35%). The medullary vasodilation induced by ET-1 was observed with doses lower than that required to produce cortical vasoconstriction; was completely blocked by bosentan, a mixed ETA/B-receptor antagonist; and was mimicked by IRL-1620, a specific ETB-receptor agonist. In contrast, BQ-123, an ETA-receptor antagonist, failed to inhibit the ET-1-dependent medullary vasodilation but effectively blocked the cortical vasoconstriction induced by the peptide. Finally, inhibition of nitric oxide (NO) synthase completely abolished, whereas cylooxygenase inhibition attenuated, the effect of ET-1 on MBF. The data demonstrate that ET-1 exerts opposite effects on renal cortical and medullary circulation, i.e., ETA-receptor-mediated cortical vasoconstriction and ETB-mediated medullary vasodilation. Furthermore, the medullary vasodilation induced by ET-1 is dependent on the NO system and, to a lesser extent, on prostaglandin generation.

Human Endothelin Subtype A Receptor Enhancement during Tissue Culture via de Novo Transcription

Neurosurgery ◽  
2002 ◽  
Vol 50 (1) ◽  
pp. 127-136 ◽  
Author(s):  
Jacob Hansen-Schwartz ◽  
Carl-Henrik Nordström ◽  
Lars Edvinsson
Keyword(s):  
Organ Culture ◽  
Receptor Antagonist ◽  
De Novo ◽  
Cerebral Arteries ◽  
Maximal Response ◽  
Messenger Ribonucleic Acid ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Eta Receptor Antagonist

ABSTRACT OBJECTIVE Endothelin (ET) has, since its discovery, increasingly been considered a key player in the pathophysiological processes of cerebral vasospasm in the course of subarachnoid hemorrhage, although it remains unclear how ET is involved. We present data that indicate an inherent capacity of human cerebral arteries to change their sensitivity to ET. METHODS Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into segments and subjected to organ culture for 48 hours. The vessels were then examined by using in vitro pharmacological methods and molecular biological techniques. RESULTS After organ culture of the cerebral arteries, both the sensitivity to and potency of ET were enhanced (maximal response, 152 ± 9%; −log (50% effective concentration), 10.3 ± 0.3), in comparison with data for fresh cerebral arteries. Contractions were inhibited by both FR139317 (a specific ETA receptor antagonist) and bosentan (a mixed ETA and ETB receptor antagonist), in a manner indicating the sole presence of contractile ETA receptors. An inconsistent dilative response to the selective ETB receptor agonist sarafotoxin 6c was observed; the response was preserved in some segments and abolished in others, and potentiation of the precontraction was observed in yet other segments. No isolated contractile response to sarafotoxin 6c was observed, however. In reverse transcription-polymerase chain reaction assays, both ETA and ETB receptor messenger ribonucleic acid was detected. CONCLUSION These results demonstrate that human cerebral arteries are capable of enhancing the function of ETA receptors.

scholarly journals Role of Endothelin-1 in the Migration of Human Olfactory Gonadotropin-Releasing Hormone-Secreting Neuroblasts

Endocrinology ◽  
2005 ◽  
Vol 146 (10) ◽  
pp. 4321-4330 ◽  
Author(s):  
Roberto G. Romanelli ◽  
Tullio Barni ◽  
Mario Maggi ◽  
Michaela Luconi ◽  
Paola Failli ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Migratory Pattern ◽  
Biochemical Analyses ◽  
Eta Receptor Antagonist ◽  
Dose Dependent

FNC-B4 neuroblasts that express both neuronal and olfactory markers have been established and cloned. These cells express GnRH and both the endothelin-1 (ET-1) gene and protein and respond in a migratory manner to GnRH in a dose-dependent manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1 by regulating the secretion of GnRH through endothelin type A receptors and by stimulating their proliferation through endothelin type B (ETB) receptors. In this study, we found that FNC-B4 cells are able to migrate in response to ET-1 through the involvement of ETB receptors. Combined immunohistochemical and biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1, through ETB receptor activation, may be required to maintain an adequate proliferative stem cell pool in the developing olfactory epithelium and the subsequent commitment to GnRH neuronal migratory pattern. The coordinate interaction between ET receptors and GnRH receptor participates in the fully expressed GnRH-secreting neuron phenotype.

Endothelin B receptors located on the endothelium provide cardiovascular protection in the hamster

2002 ◽  
Vol 103 (s2002) ◽  
pp. 280S-283S ◽  
Author(s):  
Jean-Claude HONORÉ ◽  
Caroline PROTEAU ◽  
Pedro D'ORLÉANS-JUSTE
Keyword(s):  
Receptor Antagonist ◽  
Pressor Response ◽  
Receptor Activation ◽  
Protective Role ◽  
Pressor Responses ◽  
Cardiomyopathic Hamsters ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Endothelin B ◽  
Eta Receptor Antagonist

Endothelins (ETs) act through two receptors, namely ETA and ETB. In the cardiovascular system, the activation of both receptors leads to vasoconstriction. However, ETB receptors also mediate endothelium-dependent vasodilatation and clearance of plasma ET-1. With regard to these latter properties, we wanted to assess the contribution of ETB receptors and the effects of selective and mixed ET receptor blockade on vascular tone in control Syrian Golden hamsters and in Bio 14.6 cardiomyopathic hamsters after bolus injection of ET-1 and IRL-1620, a selective ETB agonist. In 12-week-old anaesthetized control hamsters, ET-1 (0.5nmol/kg) induced a sustained pressor response which was only partly reduced by the selective ETA receptor antagonist BQ-123, suggesting a contribution of ETB receptor activation to the vasoconstrictive effects of ET-1. This was confirmed by injection of the selective ETB receptor agonist IRL-1620 (1 nmol/kg). However, the pressor response to this agonist was always preceded by a transient vasodilatation, indicating activation of endothelium-located ETB receptors. When the selective ETB receptor antagonist BQ-788 was administered, the hypotensive phase following IRL-1620 injection was abolished. Interestingly, BQ-788 or a mixture of BQ-788 and BQ-123 significantly potentiated the pressor responses to ET-1. In 12-week-old Bio 14.6 cardiomyopathic hamsters, ET-1 and IRL-1620 induced haemodynamic responses similar to those observed in control hamsters, although the IRL-1620-induced pressor increase was lower. No difference in cardiac prepro ET-1 mRNA expression was observed between the two strains of hamsters. In conclusion, we suggest that endothelium-located ETB receptors are involved in the physiological antagonism of ET-dependent protracted pressor effects, and thus may play a protective role in both normal hamsters and those with cardiomyopathy.

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