title: Thrombin-induced vascular reactivity is modulated by ETB receptor-coupled nitric oxide release in rat aorta.
abstract: The role of endothelin (ET) receptors in thrombin-induced modulation of vascular tone was evaluated by direct measurement of ET-1 and ET receptor-coupled nitric oxide (NO) release and developed isometric tension in thrombin-treated aortic rings. Here we report that rapid release of ET-1 and subsequent ETB receptor activation are required for production of the potent vasodilator NO by thrombin-stimulated aorta. Thrombin-induced NO release is ablated by pretreatment with ETB receptor antagonists or after ET receptor desensitization by repeated stimulation with ET-1. Thrombin-induced relaxation of precontracted vessels was abrogated in the presence of ETB receptor antagonists and, in contrast, marked contraction to thrombin was observed. These data indicate that the endothelium-dependent vasodilator activity previously attributed to thrombin is indirect and requires ETB receptor-coupled NO release and suggest that ET receptor modulation of thrombin-induced vascular tone may contribute to the increased vasomotor tone observed in diseased and mechanically injured vessels.
authors.affiliation: Department of Biology, Queens College, Flushing, New York, USA.
authors.forename: H I
authors.initials: HI
authors.lastname: Magazine
authors.forename: K D
authors.initials: KD
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D017466:Receptors, Endothelin; D009569:Nitric Oxide; D013917:Thrombin