Mechanisms of relaxation by urocortin in renal arteries from male and female rats.

Abstract

Urocortin is a peptide recently identified, which is structurally related to the corticotropin-releasing factor (CRF). To analyze the mechanisms that could be involved in its effect on renal arteries from male and female rats, the response to urocortin was studied in isolated segments, 2 mm long, of renal arteries from male and female rats. In renal artery segments precontracted with endothelin-1 (1 nm), urocortin (1 pm-10 nm) produced concentration-dependent relaxation, which was similar in the arteries from male and female rats. This relaxation was reduced by the antagonists of urocortin receptors astressin (1 microM) and alpha-helical CRF(9-41) (1 microM) in arteries from both male and female rats. In renal arteries from female rats, the relaxation to urocortin was reduced by the inhibitor of adenyl cyclase SQ22536 (300 microM), by 8-bromo-cyclic-ADP-ribose (cADPR; 30 microM), an antagonist of the endogenous activator of sarcoplasmic Ca2+ channel cADPR and by ryanodine (1 microM), which produces depletion of sarcoplasmic Ca2+. In renal arteries from male rats, the relaxation to urocortin was increased by ryanodine, and was not modified by SQ22536 or 8-bromo-cADPR. These results suggest that the mechanisms involved in the relaxation to urocortin in renal arteries differ between female and male rats. In female rats, this relaxation may be mediated by the production of cyclic AMP (cAMP), synthesis of cADPR and release of sarcoplasmic Ca2+, whereas in male rats it is not mediated by cAMP.