Vasodilation induced by endothelin: role of EDRF and prostanoids in rat hindquarters.
Hemodynamic responses to endothelin (ET-1) were studied in hindquarters of anesthetized rats and also in isolated buffer-perfused hindquarters of pithed rats. ET-1 (10-100 pmol ia) produced brief dose-related increases in hindquarter blood flow. Acetylcholine (ACh. 0.3-1 micrograms ia) produced similar vasodilator responses. Hemodynamic responses elicited by either ET-1 or ACh were not significantly altered by pretreatment with indomethacin. ET-1 produced dose-dependent increases in skeletal muscle microvascular perfusion, whereas ET-1 had no effect on cutaneous microvascular perfusion, suggesting that vasodilation in the skeletal muscle of the hindlimb contributes to the increase in hindquarter blood flow induced by ET-1. Hemodynamic effects of ET-1 and ACh were studied in the isolated in situ buffer-perfused hindquarters of pithed rats. ET-1 (0.01-300 pmol ia) produced only dose-dependent increases in hindquarter perfusion pressure under basal conditions or when the vascular preparation was precontracted with methoxamine. ET-1 induced vasorelaxation was not observed. ACh (3 microgram ia) produced a 64% reduction in hindquarter perfusion pressure; indicative of endothelium-dependent relaxation. ET-3 (0.1-300 pmol) produced only dose-dependent increases in hindquarter perfusion pressure. When hemodynamic effects of ET-1 were studied under conditions of constant pressure, results were similar to those obtained under constant flow. This study demonstrates that in the rat hindquarters endothelium-derived relaxing factors and prostanoids do not appear to be mediators of endothelin-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohlstein
E H
EH
Department of Pharmacology, SmithKline Beecham Research Laboratories, King of Prussia, Pennsylvania 19406-0939.
Vickery
L
L
Sauermelch
C
C
Willette
R N
RN
D000758:Anesthesia; D000818:Animals; D002021:Buffers; D016232:Endothelins / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply*; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation; D009132:Muscles / Q000098:blood supply; D009569:Nitric Oxide / Q000502:physiology*; D010477:Perfusion; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002021:Buffers; D016232:Endothelins; D011453:Prostaglandins; D014665:Vasodilator Agents; D009569:Nitric Oxide