Role of brain thromboxane A 2 in the release of noradrenaline and adrenaline from adrenal medulla in rats

Abstract

Plasma noradrenaline reflects the release from adrenal medulla and sympathetic nerves; however, the exact mechanisms of adrenal noradrenaline release remain to be elucidated. The present study was designed to characterize the source of plasma noradrenaline induced by centrally administered vasopressin and corticotropin-releasing hormone (CRH) in urethane-anesthetized rats. Intracerebroventricularly administered vasopressin (0.2 nmol/animal) and CRH (1.5 nmol/animal) elevated plasma levels of noradrenaline and adrenaline. Intracerebroventricularly administered indomethacin [1.2 μmol (500 μg)/animal] (an inhibitor of cyclooxygenase) abolished the elevations of both noradrenaline and adrenaline induced by vasopressin and CRH. Intracerebroventricularly administered furegrelate [1.8 μmol (500 μg)/animal] (an inhibitor of thromboxane A 2 synthase) abolished the elevations of both noradrenaline and adrenaline induced by vasopressin, while the reagent only attenuated the elevation of plasma adrenaline evoked by CRH. Acute bilateral adrenalectomy abolished the elevation of both noradrenaline and adrenaline induced by vasopressin, while the procedure reduced only the elevation of adrenaline induced by CRH. These results suggest that the release of noradrenaline from adrenal medulla and sympathetic nerves is mediated by different central mechanisms. The vasopressin-induced noradrenaline release from adrenal medulla is mediated by brain thromboxane A 2-mediated mechanisms, while the CRH-induced noradrenaline release from sympathetic nerves is mediated by brain prostanoid (other than thromboxane A 2)-mediated mechanisms. The vasopressin- and CRH-induced adrenaline release from adrenal medulla is also mediated by brain thromboxane A 2-mediated mechanisms in rats.