Relaxation of rat arteries by urocortin: effects of gender and diabetes

Abstract

Urocortin is a peptide recently identified, structurally related to corticotropin releasing factor (CRF). We have compared the effects of urocortin in different vascular beds, and have investigated whether there are gender differences in these effects or whether they are altered by diabetes. We have studied the response of isolated segments (2-mm long) from basilar, coronary and tail arteries to urocortin. The segments were obtained from male and female, normoglycaemic and strepto-zotocin-induced diabetic rats. In the arterial segments precontracted with endothelin-1, urocortin produced concentration-dependent relaxation, and the order of sensitivity was: tail > basilar > coronary. This relaxation was similar in arteries from male and female, diabetic and normoglycaemic rats. In tail arteries from normoglycaemic male rats, the cyclooxygenase inhibitor meclofenamate (10−5M) increased the relaxation to urocortin, and the inhibitor of nitric oxide synthesis Nω-nitro-L-arginine methyl ester (L-NAME, 10−4M) or the potassium-channel-blocker charybdotoxin (10−7M) did not modify it. In tail arteries from normoglycaemic female rats meclofenamate, charybdotoxin or L-NAME did not modify the relaxation to urocortin. These results suggested that urocortin produced vasodilation which showed regional differences between basilar, coronary and tail arteries, but was not affected by diabetes. The mechanisms underlying this relaxation in tail arteries might differ between males and females.