Pressor effects of endothelin-1 and some analogs in the perfused superior mesenteric arterial bed of the rat.
Human/porcine endothelin-1 (ET-1) dose-dependently increased perfusion pressure in both Krebs-Henseleit and blood-perfused superior mesenteric arterial bed preparations of the rat. In vitro, it was a partial agonist relative to two analogs, [Ala1,15]- and [Ala3,11]-ET-1, and the maximum response was increased by removal of the endothelium. Endothelial destruction had no effect on the responses to either [Ala1,15]- or [Ala3,11]-ET-1. [Ala1,3,11,15]-ET-1 was not an agonist in vitro but was a partial agonist relative to ET-1 and [Ala1,15]- and [Ala3,11]-ET-1 in vivo. Also, the responses to [Ala1,15]-ET-1 in the blood-perfused preparation were best described by a two-site model. These results suggest that there may be two types of receptor for these peptides. In vivo, 5 mg/kg of indomethacin potentiated the maximum response to ET-1, suggesting that its actions may be opposed by vasodilator cyclo-oxygenase products.
Hiley
C R
CR
Department of Pharmacology, University of Cambridge, England.
Douglas
S A
SA
Randall
M D
MD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D066298:In Vitro Techniques; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D010455:Peptides