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

Abstract

Diabetes mellitus reduces gender-related differences in the prevalence of cardiovascular 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 diabetics 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 rings from intact and castrated streptozotocin-diabetic rats which had been implanted with 17beta-estradiol (E2) or its vehicle for 5 days. Castration was found to attenuate contractility to noradrenaline, to enhance tone-related release of NO, as shown by curves for N-methyl-L-arginine and superoxide dismutase (SOD), and to increase endothelium-dependent relaxation to carbachol and histamine, compared with intact animals. Smooth muscle sensitivity to exogenous NO and platelet thromboxane A2 production were unchanged but prostacyclin release by aortic tissue dropped by about 40% following castration. Treatment with E2 to intact animals still attenuated contractility to noradrenaline and potentiated relaxation to SOD and histamine but affected no other parameters. In contrast, when E2 was administered to castrated animals, responses to SOD, carbachol and histamine were significantly impaired. Thus, androgen deprivation appears to improve vascular function in male diabetic rats, whereas E2 treatment exerts some beneficial effects in intact, but not in castrated animals. Our findings therefore provide new insights into the role of sex hormones in the development of diabetic vascular complications.

Circulating Sex Hormones Modulate Vascular Contractions and Acute Response to 17β-Estradiol in Rat Mesenteric Arteries

“…An increased contraction in cerebral arteries to endothelin and calcium ions but not phenylephrine and U46619 has also been reported [42] . Our results showing a decrease in contraction to phenylephrine in both male and female rats after 14 days of 17 ␤ -estradiol treatment is in line with other studies [5,43,44] .…”

Metabolic Predictors of Change in Vascular Function

“…35 In those affected by diabetes mellitus and insulin resistance, vascular dysfunction has been associated with decreased endothelial NO production, higher oxidative stress and increased accumulation of advanced glycation end products and expression of receptor of advanced glycation end products. 36,37 Circulating advanced glycation end products disrupt cell-extracellular matrix and matrix-matrix interactions and increase collagen cross-linking, potentially leading to an increase in vascular stiffness. 38,39 Similar to glycemia, previous studies on lipid associations to vascular function have been equivocal, with some demonstrating baseline HDL and triglyceride values were associated with aortic stiffness, whereas others showed no association.…”

Risk factors for cardiovascular disease in women with diabetes

“…Based on this assumption, it would be reasonable to think that hormone supplementation to restore the normal testosterone/estrogen ratio would be beneficial in women with type 2 diabetes with CVD complications. Indeed, a few studies have shown that hormone therapy in women with type 2 diabetes is associated with a reduction in visceral adiposity and improvement in lipid and glucose metabolism, all of which are risk factor of CVD 58–60 . While the precise mechanisms by which sex hormones exert their effects and contribute to development of CVD are still being investigated, both clinical and experimental studies suggest that sex hormones are important regulators of fat, glucose and lipid metabolism, blood pressure, cardiovascular and renal function 55–56, 61–64 .…”