Thrombin-induced vascular reactivity is modulated by ETB receptor-coupled nitric oxide release in rat aorta.
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.
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Department of Biology, Queens College, Flushing, New York, USA.
Srivastava
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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*
D017466:Receptors, Endothelin; D009569:Nitric Oxide; D013917:Thrombin