Aldosterone and the vasculature: mechanisms mediating resistant hypertension

The renin-angiotensin-aldosterone system appears to be one of the key factors in the development of hypertensive vascular disease. Identification of mineralocorticoid receptors in the heart, vasculature, and brain has raised speculation that aldosterone may directly mediate its detrimental effects in these target organs independent of angiotensin II. Aldosterone increases vascular tone due to endothelial dysfunction and enhances the pressor response to catecholamines and up-regulation of angiotensin II receptors. It induces electrolyte transport over the vascular smooth cell membrane and plays a crucial role in vascular remodeling of small and large arteries. Moreover, aldosterone is involved in vascular injury and promotes collagen synthesis, which leads to increased arterial stiffness and elevation of blood pressure. Aldosterone has also been shown to exert a number of effects in the central nervous system. Several human studies have shown that aldosterone is related to baroreflex resetting. Thus, in cases of severe hypertension, there would be fewer compensatory mechanisms to offset blood pressure elevation and ensuing vascular damage. Endothelial and vascular smooth muscle cells have the potential to synthesize aldosterone, and tissue aldosterone could play a more important role in resistant hypertension and target organ damage than circulating aldosterone. Understanding aldosterone synthase polymorphism may provide insight into blood pressure patterns and their consequences. Understanding the vascular mechanisms of aldosterone in resistant hypertension may explain why selective aldosterone receptor blockers might have beneficial effects in resistant hypertension.