Sympathetic and Renin–Angiotensin Activity in the Pathophysiology of Hypertension

Abstract

The implication of the sympathetic nervous system (SNS) in the pathogenesis of essential hypertension has been suggested a long time ago, considering the major role played by this system in blood pressure (BP) regulation. Studies based on both global (e.g., plasma norepinephrine) and regional (norepinephrine spillover and microneurography) assessments of sympathetic activity have demonstrated that neurogenic mechanisms may be involved in up to 50 % of all cases of essential hypertension. In addition, renal sympathetic denervation has been shown to induce signifi cant and persistent decreases in BP. Moreover, there is evidence that sympathetic hyperactivity may contribute directly to target-organ damage, including cardiac hypertrophy, vascular remodeling, and renal dysfunction. The specifi c causes of sympathetic activation in essential hypertension are not entirely known, but genetic factors, high dietary salt intake, as well as several metabolic and neurohumoral abnormalities have been involved. In patients with obesity-and metabolic syndrome-associated hypertension, SNS overactivity may result from many factors, including hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, hypoghrelinemia, and RAAS activation.The renin-angiotensin system (RAS) is another key regulator of BP and fl uid homeostasis. Ang II induces BP elevation by vasoconstriction of renal and systemic arterioles, stimulation of renal tubular sodium reabsorption, and release of aldosterone from the adrenal glands. Moreover, both Ang II (via AT 1 receptors) and aldosterone exert proinfl ammatory, profi brotic, and prooxidant effects on the cardiovascular system, contributing to myocardial hypertrophy and fi brosis, vascular remodeling and calcifi cation, cerebrovascular damage, and renal glomerular and tubulointerstitial injury. In contrast, other components of the RAS, including mainly the AT 2 receptors and the ACE2/Ang-(1-7)/Mas axis, counteract most of the negative cardiovascular effects of the Ang II/AT 1 /aldosterone system and might play a compensatory role in hypertension.