Role of endothelium in endothelin-evoked contractions in the rat aorta.
We designed experiments to determine the role of endothelium-derived contracting factor or factors in the response to endothelin-1 and endothelin-3 in the aorta of normotensive and hypertensive rats. Rings of thoracic aortas, with and without endothelium, from normotensive and spontaneously hypertensive rats were suspended in organ chambers for recording of isometric tension in the presence of nitro-L-arginine, an inhibitor of nitric oxide synthase. The removal of endothelium decreased the contractions evoked by both endothelins in the aorta of spontaneously hypertensive but not of normotensive rats. Indomethacin (inhibitor of cyclooxygenase), dazoxiben (inhibitor of thromboxane synthase), and SQ-29,548 (antagonist of thromboxane A2 receptors) reduced, in aortic rings of spontaneously hypertensive rats, the contractions to endothelins in rings with but not in those without endothelium, whereas their effect was not endothelium-dependent in tissues of normotensive rats. BQ-123, a selective endothelin-A receptor antagonist, shifted the concentration-response curve to endothelin-1 to the right in a concentration-dependent manner and abolished the endothelium-dependent component of the contractions evoked by the peptide. The presence of the endothelium increased the basal and endothelin-stimulated release of thromboxane B2, the stable metabolite of thromboxane A2, in aortas of spontaneously hypertensive rats but not in those of normotensive rats. These data suggest that endothelium-derived thromboxane A2 contributes to contractions evoked by endothelin-1 and endothelin-3 in the aorta of the spontaneously hypertensive rat but not in that of the normotensive rat. Both the receptors on the endothelial cells (mediating the release of thromboxane A2) and those on vascular smooth muscle belong to the endothelin-A subtype.
Taddei
S
S
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030.
Vanhoutte
P M
PM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013929:Thromboxane B2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016232:Endothelins; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D013929:Thromboxane B2; C045749:SQ 29548; D007213:Indomethacin