Endothelin ET B receptors counteract venoconstrictor effects of endothelin-1 in anesthetized rats

Abstract

The inhibitory effects of BQ 788 (3 mg/kg, i.v., ET B-receptor antagonist) on endothelin-1 (ET-1)- or IRL 1620 (ET B-receptor agonist)-induced changes in mean arterial pressure (MAP), mean circulatory filling pressure (MCFP, driving force of venous return), arterial resistance (R A), venous resistance (R V) and cardiac output (CO) were characterized in 6 groups of pentobarbital-anesthetized rats. ET-1 or IRL 1620 (0.5, 1 and 2 nmol/kg, i.v.) dose-dependently increased MAP, R A, R V and MCFP and decreased CO. Maximum changes in R A, R V and CO elicited by ET-1 were greater than those by IRL 1620. Equimolar doses of ET-1 and IRL 1620 also caused similar initial transient decreases in MAP. BQ 788 alone slightly elevated MCFP, but did not alter other variables. The ET B-blocker abolished all changes elicited by IRL 1620, but only partially inhibited its responses on MCFP, showing the presence of BQ 788-insensitive receptors. BQ 788 also abolished ET-1's depressor response, partially inhibited its effect on MCFP, and markedly augmented its effects on R A, R V and CO. Thus, ET B-receptors counteract the sustained constrictor effects of ET-1 on arterial and venous resistance vessels. Our results indicate a substantial arterial and venous dilator role for ET B receptors.