Endothelin ET(B) receptors counteract venoconstrictor effects of endothelin-1 in anesthetized rats.
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 (RA), venous resistance (RV) 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, RA, RV and MCFP and decreased CO. Maximum changes in RA, RV 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 RA, RV 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.
Department of Pharmacology & Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
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B
Palacios
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Lim
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CC
Pang
D000758:Anesthesia; D000818:Animals; D019332:Endothelin-1 / Q000037:antagonists & inhibitors*; D016232:Endothelins / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins / Q000187:drug effects* / Q000502:physiology
D019332:Endothelin-1; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C074308:sovateltide; C086539:BQ 788