The protective role of estrogen and brain estrogen receptors in the pathogenesis of hypertension

Hypertension (HT) is the most prevalent cardiovascular disease. It is recognized that the sympathetic nervous system plays an important role in the pathogenesis of HT. Prior to the end of menopause women have lower arterial blood pressure (BP) in comparison to men of comparable ages. However, after menopause, the rate of rise in female BP accelerates and quickly reaches levels comparable to those of men. It is hypothesized that the female increase in BP is the result of estrogen loss. Estrogen is likely to exert its antihypertensive actions at several sites in the body, including blood vessels, heart, kidneys, and importantly, the brain. Preclinical studies indicate that estrogen produces its protective effects in the brain by interacting with different types of estrogen receptors located in various sites in the central neural network controlling sympathetic tone. The protective effects of estrogen in the brain involve cellular mechanisms associated with antiinflammatory actions reducing reactive oxygen species and activation of the antihypertensive arm of the renin-angiotensin-aldosterone system. Estrogen not only protects against the effects of short-term treatments that increase BP, but also against changes in sustained brain neuroplasticity that result in sensitization of the hypertensive response. Sensitization of the hypertensive response predisposes an individual toward an enhanced rise in BP to subsequently encountered stressors. Increased understanding of the protective actions that are mediated by estrogen on different types of estrogen receptors and their location in the brain holds promise for developing therapeutic strategies for the prevention and treatment of HT.