Diabetes abolishes the vascular protective effects of estrogen in female rats

Estrogen is known to exert a protective effect against cardiovascular disea se. However, women with diabetes have three times the risk as compared with age-matched non-diabetic women. Our previous study on aortic rings of ovar iectomized (OVX) female rats treated with 17-beta-estradiol (E-2) demonstra ted that the beneficial effect of estrogen is related to the basal release of NO from endothelial cells. In the present study, in order to understand why estrogen protection is abolished in diabetes, we tested vascular respon ses in OVX, streptozotocin-diabetic female rats and their non-diabetic cont rols receiving or not E-2 replacement. Concentration-response curves to nor epinephrine (NE) showed attenuation of the contractile response in E-2-trea ted diabetic, with respect to non-diabetic preparations. This response was further impaired in diabetic, E-2-deprived rats. The basal release of NO, a s evaluated by concentration-related responses to N-G-methyl-L-arginine ace tate in NE precontracted aortic rings, was found to be impaired in E-2-trea ted diabetic rats, no further effect being induced by E-2 deprivation. The endothelium-dependent relaxation produced by carbachol did not change betwe en groups, whereas the relaxation produced by histamine was enhanced by bot h diabetes and E-2 deprivation. However, E-2 treatment counteracted. the re sponse to histamine only in preparations from non-diabetic animals. Finally , the relaxation induced by sodium nitroprusside, an endothelium-independen t relaxant agent, was comparable between groups. These findings suggest tha t the lack of protective effects of estrogen in diabetes may be mainly ascr ibed to the failure of estrogen to reverse the impaired basal release of NO and the abnormal relaxation to histamine, which are observed in the aorta of diabetic rats.