Chronic pressure-mediated baroreflex activation suppresses renal sympathetic nerve activity. Recent observations indicate that chronic electrical activation of the carotid baroreflex produces sustained reductions in global sympathetic activity and arterial pressure. Thus, we investigated the effects of global and renal specific suppression of sympathetic activity in dogs with sympathetically-mediated, obesity-induced hypertension by comparing the cardiovascular, renal, and neurohormonal responses to chronic baroreflex activation and bilateral surgical renal denervation. After control measurements, the diet was supplemented with beef fat while sodium intake was held constant. After 4 weeks on the high-fat, when body weight had increased ~a 50%, fat intake was reduced to a level that maintained this body weight. This weight increase was associated with an increase in mean arterial pressure from 100±2 to 117±3 mm Hg and heart rate from 86±3 to 130±4 bpm. The hypertension was associated with a marked increase in cumulative sodium balance despite ~ a 35% increase in GFR. The importance of increased tubular reabsorption to sodium retention was further reflected by ~ a 35% decrease in fractional sodium excretion. Subsequently, both chronic baroreflex activation (7 days) and renal denervation decreased plasma renin activity and abolished the hypertension. However, baroreflex activation also suppressed systemic sympathetic activity and tachycardia and reduced glomerular hyperfiltration while increasing fractional sodium excretion. In contrast, GFR increased further after renal denervation. Thus, by improving autonomic control of cardiac function and diminishing glomerular hyperfiltration, suppression of global sympathetic activity by baroreflex activation may have beneficial effects in obesity beyond simply attenuating hypertension.

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Vascular complications are a leading cause of morbidity and mortality in both men and women with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus, however the prevalence, progression and pathophysiology of both microvascular (nephropathy, neuropathy and retinopathy) and macrovascular [coronary heart disease (CHD), myocardial infarction, peripheral arterial disease (PAD) and stroke] disease are different in the two sexes. In general, men appear to be at a higher risk for diabetic microvascular complications, while the consequences of macrovascular complications may be greater in women. Interestingly, in the absence of diabetes, women have a far lower risk of either micro- or macro-vascular disease compared with men for much of their lifespan. Thus, the presence of diabetes confers greater risk for vascular complications in women compared with men and some of the potential reasons, including contribution of sex hormones and sex-specific risk factors are discussed in this review. There is a growing body of evidence that sex hormones play an important role in the regulation of cardiovascular function. While estrogens are generally considered to be cardioprotective and androgens detrimental to cardiovascular health, recent findings challenge these assumptions and demonstrate diversity and complexity of sex hormone action on target tissues, especially in the setting of diabetes. While some progress has been made toward understanding the underlying mechanisms of sex differences in the pathophysiology of diabetic vascular complications, many questions and controversies remain. Future research leading to understanding of these mechanisms may contribute to personalized- and sex-specific treatment for diabetic micro- and macro-vascular disease.