ENDOTHELIN ETB RECEPTORS COUNTERACT VENOCONSTRICTOR EFFECTS OF ENDOTHELIN-1 IN ANESTHETIZED RATS

The inhibitory effects of BQ 788 (3 mg/kg, i.v., ETB-receptor antagoni st) on endothelin-1 (ET-1)- or IRL 1620 (ETB-receptor agonist)-induced changes in mean arterial pressure (MAP), mean circulatory filling pre ssure (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 M CFP and decreased CO. Maximum changes in R-A, R-V and CO elicited by E T-1 were greater than those by IRL 1620. Equimolar doses of ET-1 and I RL 1620 also caused similar initial transient decreases in MAP. BQ 788 alone slightly elevated MCFP, but did not alter other variables: The ETB-blocker abolished all changes elicited by IRL 1620, but only parti ally inhibited its responses on MCFP, showing the presence of BQ 788-i nsensitive receptors. BQ 788 also abolished ET-1's depressor response, partially inhibited its effect on MCFP, and markedly augmented its ef fects on R-A, R-V and CO. Thus, ETB-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 ETB-receptors.