Effect of endothelin-1 and BQ 123 on arterioles and venules of hypertensive rats.
We investigated the effect of the ETA-receptor antagonist BQ 123 (1.0, 5.0, and 10 mg/kg/h i.v.) on the endothelin-1 (ET-1) (10(-8) M)-induced vasoconstriction of arterioles in the cremaster muscle preparation of anesthetized SHRs. ET-1 10(-8) M led to a constriction of the arterial microvessels most marked in A4 arterioles (-92.9%) and least marked in A1 (-17.3%). The ET-1-induced constriction of venules was much less pronounced and showed no dependence on the vessel type. BQ 123 1.0 mg/kg/h was ineffective in antagonizing the vasoconstrictor effect of ET-1 in arterioles. With 5.0 mg/kg/h BQ 123, the ET-1-induced arterial vasoconstriction was inhibited by 68% in A4, by 44% in A3, by 39% in A2, and by 10% in A1 arterioles. BQ 123 10 mg/kg/h blocked the vasoconstrictor effect of ET-1 in all arteriole types by 79-93% and also reduced diastolic blood pressure in SHRs significantly at the end of the infusion period (-12.6 mm Hg). The ET-1-induced slight venous constriction was not affected by BQ 123.
Hergenröder
S
S
Knoll AG, Ludwigshafen, Germany.
Münter
K
K
Kirchengast
M
M
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014661:Vasoconstriction / Q000187:drug effects*; D014699:Venules / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)