Effects of a Potent, Nonselective Endothelin Receptor Antagonist, [Thr18, γ-MeLeu19]-Endothelin-1, on the Isolated Blood Vessels

1995 ◽  
Vol 212 (2) ◽  
pp. 421-427 ◽  
Author(s):  
H. Karaki ◽  
S.A. Sudjarwo ◽  
N. Shimamoto ◽  
M. Wakimasu ◽  
M. Fujino
Keyword(s):  
Receptor Antagonist ◽  
Blood Vessels ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Endothelin 1

Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition prevents endothelin A receptor antagonism in rat aorta

2007 ◽  
Vol 292 (4) ◽  
pp. H1961-H1966 ◽  
Author(s):  
M. Tosun ◽  
Y. Erac ◽  
C. Selli ◽  
N. Karakaya
Keyword(s):  
Endoplasmic Reticulum ◽  
Receptor Antagonist ◽  
Cyclopiazonic Acid ◽  
Rat Aorta ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Atpase Inhibitor ◽  
Endothelin 1 ◽  
Endothelin A Receptor ◽  
Endothelin A

This study tested whether sarcoplasmic-endoplasmic reticulum Ca2+-ATPase regulates the ability of endothelin receptor antagonist to inhibit the endothelin-1 constriction. The endothelin A receptor antagonist BQ-123 (1 μM) completely relaxed constriction to 10 nM endothelin-1 in endothelium-denuded rat aorta. Challenge with cyclopiazonic acid (10 μM), a sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibitor, during the plateau of endothelin-1 constriction enhanced the constriction by ∼30%. BQ-123 relaxed the endothelin-1 plus cyclopiazonic acid constriction by only ∼10%. In contrast, prazosin (1 μM), an α-adrenergic receptor antagonist, still completely relaxed the 0.3 μM phenylephrine constriction in the presence of cyclopiazonic acid. Verapamil relaxed the endothelin-1 plus cyclopiazonic acid constriction by ∼30%, whereas Ni2+ and 2-aminoethoxydiphenyl borate, nonselective cation channel and store-operated channel blockers, respectively, completely relaxed the constriction. These results suggest that lowered sarcoplasmic-endoplasmic reticulum Ca2+-ATPase activity selectively decreases the ability of endothelin receptor antagonist to inhibit the endothelin A receptor. The decreased antagonism may be related to the opening of store-operated channels and subsequent greater internalization of endothelin A receptor.

Endothelin-1 expression in blood vessels of DOCA-salt hypertensive rats treated with the combined ETA/ETB endothelin receptor antagonist bosentan

1995 ◽  
Vol 73 (3) ◽  
pp. 390-398 ◽  
Author(s):  
Richard Larivière ◽  
Pavol Sventek ◽  
Gaétan Thibault ◽  
Ernesto L. Schiffrin
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Receptor Antagonist ◽  
Blood Vessels ◽  
Thoracic Aorta ◽  
Mesenteric Arteries ◽  
Endothelin Receptor ◽  
Hypertensive Rats ◽  
Endothelin 1 ◽  
Wet Weight

In previous studies it has been shown that blood vessels of deoxycorticosterone acetate (DOCA) salt hypertensive rats present significantly higher immunoreactive ET-1 (ir-ET-1) content and increased ET-1 gene expression. DOCA-salt hypertensive rats respond to treatment with the combined ETA/ETB endotheiin receptor antagonist bosentan with lowering of blood pressure. In the present study, we investigated the ir-ET-1 levels and the expression of the ET-1 gene in blood vessels of DOCA-salt hypertensive rats treated or not treated with bosentan. Blood pressure was significantly lower in bosentan-treated rats (185 ± 6 mmHg; 1 mmHg = 133.3 Pa) compared with DOCA-salt hypertensive rats (203 ± 4 mmHg; p < 0.01). Plasma ir-ET-1 concentration was slightly but significantly elevated (p < 0.01) in DOCA-salt hypertensive rats compared with uninephrectomized control rats, and was further increased (p < 0.01) in bosentan-treated rats. The tissue wet weight and ir-ET-1 content of segments of thoracic aorta were significantly increased (p < 0.01) in DOCA-salt hypertensive rats in comparison with control rats, but were similar in bosentan-treated DOCA-salt rats. The abundance of ET-1 mRNA measured by Northern blot analysis in thoracic aorta and the ir-ET-1 content were attenuated by bosentan treatment. Tissue wet weight and ir-ET-1 content in the mesenteric vascular bed were similar in bosentan-treated and -untreated DOCA-salt rats, and were significantly higher in both groups than in control rats (p < 0.01). ET-1 mRNA levels were increased in mesenteric arteries of DOCA-salt hypertensive rats and were further enhanced by bosentan treatment. These data suggest that inhibition of ETA and ETB receptor mediated ET-1 responses by bosentan has a slight but beneficial effect on blood pressure of DOCA-salt hypertensive rats. Chronic blockade of both ET receptors results in increased circulating levels of ET-1 and attenuated ET-1 expression and vascular hypertrophy in aorta but not in the mesenteric vasculature. ET-1 may be involved in the maintenance of elevated blood pressure in DOCA-salt hypertension and perhaps other experimental models of hypertension in the rat in part through a vascular hypertrophic effect.Key words: endothelin-1, endothelin receptor antagonist, aorta, mesenteric arteries, immunoreactive ET-1, preproET-1 mRNA, gene expression.

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