1447: The Effects of Endothelin-1 and YM598, a Novel Selective Endothelin Eta Receptor Antagonist, on the Lower Urinary Tract in Vitro (Rabbit Tissue) and in Vivo (Dogs)

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.

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Ontogeny of Big endothelin-1 effects in newborn piglet pulmonary vasculature

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.265.1.h139 ◽

1993 ◽

Vol 265 (1) ◽

pp. H139-H145 ◽

Cited By ~ 2

Author(s):

S. Liben ◽

D. J. Stewart ◽

J. De Marte ◽

T. Perreault

Keyword(s):

Endothelial Cells ◽

Pulmonary Vasculature ◽

Converting Enzyme ◽

Endothelin 1 ◽

Amino Acid Peptide ◽

Eta Receptor ◽

Eta Receptor Antagonist ◽

Dose Dependent

Endothelin-1 (ET-1), a 21-amino acid peptide produced by endothelial cells, results from the cleavage of preproendothelin, generating Big ET-1, which is then cleaved by the ET-converting enzyme (ECE) to form ET-1. Big ET-1, like ET-1, is released by endothelial cells. Big ET-1 is equipotent to ET-1 in vivo, whereas its vasoactive effects are less in vitro. It has been suggested that the effects of Big ET-1 depend on its conversion to ET-1. ET-1 has potent vasoactive effects in the newborn pig pulmonary circulation, however, the effects of Big ET-1 remain unknown. Therefore, we studied the effects of Big ET-1 in isolated perfused lungs from 1- and 7-day-old piglets using the ECE inhibitor, phosphoramidon, and the ETA receptor antagonist, BQ-123Na. The rate of conversion of Big ET-1 to ET-1 was measured using radioimmunoassay. ET-1 (10(-13) to 10(-8) M) produced an initial vasodilation, followed by a dose-dependent potent vasoconstriction (P < 0.001), which was equal at both ages. Big ET-1 (10(-11) to 10(-8) M) also produced a dose-dependent vasoconstriction (P < 0.001). The constrictor effects of Big ET-1 and ET-1 were similar in the 1-day-old, whereas in the 7-day-old, the constrictor effect of Big ET-1 was less than that of ET-1 (P < 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

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Obstruction-induced alterations within the urinary bladder and their role in the pathophysiology of lower urinary tract symptomatology.

Canadian Urological Association Journal ◽

10.5489/cuaj.1636 ◽

2014 ◽

Vol 8 (7-8) ◽

pp. 524 ◽

Cited By ~ 11

Author(s):

Christos Komninos ◽

Iraklis Mitsogiannis

Keyword(s):

Urinary Tract ◽

Lower Urinary Tract ◽

Bladder Wall ◽

Outlet Obstruction ◽

Prostatic Hyperplasia ◽

Animal Tissue ◽

Urinary Tract Symptoms ◽

Lower Urinary

Benign prostatic hyperplasia (BPH) is considered a frequent cause of bladder outlet obstruction (BOO) and lower urinary tract symptoms. This review addresses the bladder response to BOO and focuses on the alterations and biochemical adaptability of the bladder wall in the presence of hypoxia. A literature review of published articles has been performed, including both in vivo and in vitro studies on human and animal tissue.

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Effects of inhibition of the l-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1992.tb14483.x ◽

1992 ◽

Vol 107 (1) ◽

pp. 178-184 ◽

Cited By ~ 153

Author(s):

K. Persson ◽

Y. Igawa ◽

A. Mattiasson ◽

K.-E. Andersson

Keyword(s):

Nitric Oxide ◽

Urinary Tract ◽

Lower Urinary Tract ◽

Nitric Oxide Pathway ◽

Lower Urinary

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

Endocrinology ◽

10.1210/endo.138.10.5448 ◽

1997 ◽

Vol 138 (10) ◽

pp. 4358-4363 ◽

Cited By ~ 2

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.

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