title: Comparative sensitivities of isolated rat renal arterioles to endothelin.
abstract: The specific intrarenal sites and mechanism of endothelin (ET) vascular action are controversial. In this study afferent (AA) and efferent arterioles (EA) were isolated from the kidneys of normal Sprague-Dawley rats. Their respective concentration-dependent changes in lumen diameter in response to ET-1 were compared with those of angiotensin II (ANG II) and norepinephrine (NE). In a second series of experiments, the duration of vasoconstriction to comparable transient submaximal ET-1, ANG II, and NE concentrations in AA and EA was examined. The role of angiotensin II in mediating endothelin vasoconstriction also was examined with the converting-enzyme inhibitor captopril (CAP) and the competitive inhibitor [Sar1,Ala8]ANG II (SAR). The half-maximal constriction concentration (EC50) of ET-1 was less in EA than AA (P < 0.01). EC50 of ET-1 in AA was similar to that of ANG II, but was less than that of NE (P < 0.001). In EA the EC50 of ET-1 was also similar to that of ANG II, but much less than that of NE (P < 0.001). In both AA and EA the duration of ET-1 constriction was at least twice that of ANG II and more than fivefold that of NE. Neither CAP (10(-6) M) nor SAR (10(-7) M) changed the vasoconstrictor response to submaximal concentrations of ET-1 in AA or EA. It is concluded that ET-1 is a potent and prolonged constrictor agonist with a small, but significantly greater, concentration-dependent effect in EA than AA. The constrictor effect of ET-1 does not require ANG II activity.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver.
authors.forename: D M
authors.initials: DM
authors.lastname: Lanese
authors.forename: B H
authors.initials: BH
authors.lastname: Yuan
authors.forename: I F
authors.initials: IF
authors.lastname: McMurtry
authors.forename: J D
authors.initials: JD
authors.lastname: Conger
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D012504:Saralasin / Q000494:pharmacology; D014661:Vasoconstriction
chemical_list: D016232:Endothelins; D000804:Angiotensin II; D012504:Saralasin; D009638:Norepinephrine