Coronary action of endothelin-1 and vasopressin during acute hypertension in anesthetized goats. Role of nitric oxide and prostanoids.

摘要

Coronary reactivity to endothelin-1 and vasopressin during acute, moderate hypertension, and the role of nitric oxide (NO) and prostanoids in this reactivity was examined in anesthetized goats. Left circumflex coronary flow was electromagnetically measured, and hypertension was induced by constriction of the thoracic aorta in animals nontreated (7 goats) or treated with the inhibitor of NO synthesis N(w)-nitro-l-arginine methyl esther (l-NAME, 6 goats) or the cyclooxygenase inhibitor meclofenamate (6 goats). Under normotension (19 animals), basal mean values for mean arterial pressure and coronary vascular conductance (CVC) were 89+/-3 mm Hg and 0.36+/-0.038 ml/min/mm Hg, respectively. Endothelin-1 (0.01-0.3 nmol) and vasopressin (0.03-1 mug) dose-dependently decreased CVC, which, for endothelin-1 ranged from 5+/-1% (0.01 nmol; P<0.01) to 66+/-4% (0.3 nmol; P<0.001) and for vasopressin ranged from 9+/-1% (0.03 mug P<0.01) to 41+/-3% (1 mug; P<0.001). During nontreated and treated hypertension, mean arterial pressure increased to approximately 130 mm Hg (P<0.01), and CVC decreased (17%) only during l-NAME-treated hypertension. The effects of endothelin-1 and vasopressin on CVC were decreased by approximately 50% during nontreated hypertension, and this was abolished by l-NAME and was not affected by meclofenamate. Therefore, during acute, moderate hypertension, the coronary vasoconstriction to endothelin-1 and vasopressin is attenuated, which may be related with increased NO release but not with prostanoids.