The influence of sex hormones on vascular responses in the aorta of streptozotocin-diabetic male rats

Diabetes mellitus reduces fender-related differences in the prevalence of c ardiovascular disease by fading the vascular protective effects afforded by estrogen in females. However, the impact of estrogen treatment on and the contribution of androgens to vascular function in vessels from male diabeti cs are largely unknown. We investigated the effects of androgen deficiency and in vivo estrogen treatment by assessing the responsiveness to a number of vasoactive agents and the formation of eicosanoid mediators in aortic ri ngs from intact and castrated streptozotocin-diabetic rats which had been i mplanted with 17 beta-estradiol (E-2) or its vehicle for 5 days. Castration was found to attenuate contractility to noradrenaline, to enhance tone-rel ated release of NO. as shown by curves for N-methyl-L-arginine and superoxi de dismutase (SOD), and to increase endothelium-dependent relaxation to car bachol and histamine, compared with intact animals. Smooth muscle sensitivi ty to exogenous NO and platelet thromboxane A(2) production were unchanged but prostacyclin release by aortic tissue dropped by about 40% Following ca stration. Treatment with E-2 to intact animals still attenuated contractili ty to noradrenaline and potentiated relaxation to SOD and histamine but aff ected no other parameters. In contrast, when E-2 was administered to castra ted animals, responses to SOD, carbachol and histamine were significantly i mpaired. Thus: androgen deprivation appears to improve vascular function in male diabetic rats, whereas E-2 treatment exerts some beneficial effects i n intact, but not in castrated animals. Our findings therefore provide new insights into the role of sex hormones in the development of diabetic vascu lar complications.