Bradykinin and pituitary-adrenocortical function in the rabbit: in vitro and in vivo studies

Bradykinin (BK) is a 9-amino acid peptide, which has been found to affect adrenocortical secretion in the calf and rat. We investigated the in vitro and in vivo effects of BK and its receptor antagonist [D-Arg, (Hyp3,D-Phe7)]-BK (BK-A) on pituitary-adrenocortical function in the rabbit. BK and BK-A raised basal release of aldosterone, but not of corticosterone by dispersed zona glomeralosa and zona fasciculata-reficularis cells, respectively. Both peptides did not affect ACTH-stimulated aldosterone secretion. Conversely, BK concentration-dependently decreased ACTH-stimulated corticosterone production, and BK-A annulled this effect. The bolus intravenous injection of BK did not alter plasma ACTH concentration. However, BK lowered the blood concentration of both aldosterone and corticosterone, as well as the overall production of the two hormones over a period of 90 min after its administration. The simultaneous injection of BK-A blocked these effects of BK. BK-A alone did not evoke any sizeable change in blood hormonal levels. Collectively, these findings allow us to conclude that in rabbits (i) exogenous BK depresses adrenocortical secretion, through a receptor-mediated mechanism, which does not involve the inhibition of pituitary ACTH release-, and (ii) endogenous BK-like peptides do not play a relevant role in the functional regulation of the pituitary-adrenal axis, at least under basal conditions.