Role of ET(A) and ET(B) receptors in endothelin-1-induced adrenal catecholamine secretion in vivo

The present study was designed to test whether endothelin (ET) A and/or B receptors in the adrenal medulla are functionally involved in ET-1-induced catecholamine (CA) release in anesthetized dogs. ET-1 was locally infused into the gland via the left adrenolumbar artery. Plasma CA in adrenal venous and aortic blood was determined by a high-performance liquid chromatography method. In the control group, the local infusion of ET-1 (0.5 1-18, 0.4 mu M) resulted in a significant increase in CA output. In the presence of a low dose of BQ-123 (5 mu g, 16.4 mu M), the ET-1-induced CA response was significantly attenuated by similar to 80%. With a high dose of BQ-123 (50 mu g, 164 mu M), the CA response was further blocked by similar to 95%. This inhibition was significantly greater than that obtained with the low dose of BQ-123. By contrast, a low dose of BQ-788 (5 mu g, 15.1 mu M) did not significantly affect the CA response. With a high dose of BQ-788 (50 mu g, 151 mu M), the CA response was only partially inhibited by similar to 70%. The results indicate that BQ-123 significantly inhibited ET-1-induced adrenal CA release in a dose-dependent manner. With the low doses, the CA response was markedly inhibited by BQ-123 but remained unchanged in the presence of BQ-788. Moreover, the high dose of BQ-123 virtually abolished the CA response, whereas BQ-788 failed to do so within the dose range tested. The present study suggests that the ETA receptor may play a predominant role in mediating the ET-1-induced CA secretion in the canine adrenal gland in vivo, although the possible involvement of the ET(B) receptor could not completely be excluded under the present experimental conditions.