The basal and stimulated release of EDRF inhibits the contractions evoked by endothelin-1 and endothelin-3 in aortae of normotensive and spontaneously hypertensive rats.
Endothelin-1 (ET-1) evoked concentration-dependent contractions that were slow in onset and sustained in aortae from both normotensive (Wistar and Wistar-Kyoto rats) and spontaneously hypertensive rats. The presence of a functional endothelium reduced the contractions evoked by low concentrations of ET-1 in the aortae from normotensive rats and shifted the concentration-contraction curves to the right in the hypertensive rat. NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide (NO) synthase, inhibited the influence of the endothelium. Endothelin-3 (ET-3) evoked contractions in aortae from both normotensive and hypertensive rats at concentrations greater than 3 x 10(-8) M, which were reduced by the presence of a functional endothelium. ET-1 and ET-3 evoked concentration- and endothelium-dependent relaxations in aortae contracted submaximally with phenylephrine, from both types of rats. The relaxations were reversed by methylene blue, an inhibitor of soluble guanylate cyclase, and nitro-L-arginine, a competitive inhibitor of NO synthase. These observations demonstrate that the endothelium modulates the contractile response evoked by ET-1 and ET-3 in the aorta of the rat. This inhibition is more pronounced in aortas from hypertensive compared to normotensive rats and is mediated, at least in part, by an enhanced production of endothelium-derived NO.
Schini
V B
VB
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030.
Kim
N D
ND
Vanhoutte
P M
PM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016232:Endothelins / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013268:Stimulation, Chemical; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D009569:Nitric Oxide