[Bosentan attenuates the hypertensive effect of angiotensin II in rats].
The influence of nonspecific blockade of endothelin receptors by bosentan (30 mg/kg per day, gavage) was assessed on hypertension induced by infusion of angiotensin II (AngII 200 ng/kg/min sc for 10 days) in rats. Tail-cuff pressure was measured before and every second day of AngII-infusion period. At the end of experiments, mean arterial pressure (MAP, mmHg), cardiac output (CO ml/min/kg body weight) and renal blood flow (RBF ml/min/g kidney weight) were determined (microspheres technique) in conscious rats, and total peripheral and renal vascular resistances were calculated (TPR = MAP/CO and RVR = MAP/RBF). [table: see text] Tail-cuff pressure increased from 126 +/- 4 to 164 +/- 8 mmHg in rats infused with AngII alone whereas it did not change (basal: 132 +/- 3 and final: 135 +/- 3 mmHg: p = NS) when bosentan was coadministered with AngII. At the end of study in conscious rats, the AngII-induced rise in MAP was accompanied by a reduction in CO and RBF and a marked increased in TPR and RVR. In AngII-perfused rats, CO, RBF, TPR and RVR were restored by bosentan to values observed in untreated rats. These results indicate that blockade of endothelin A and B receptors by bosentan prevents the development of AngII-induced hypertension through attenuation of the effect of AngII on vascular tone and suggest that endothelin is an important mediator of the vasoconstrictor action of angiotensin II in rats.
Herizi
A
A
Groupe rein et hypertension, centre hospitalier universitaire de Montpellier.
Jover
B
B
Mimran
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000077300:Bosentan; D004195:Disease Models, Animal; D004347:Drug Interactions; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000804:Angiotensin II; D000077300:Bosentan