The role of Rho protein signaling in hypertension.

Arterial hypertension is a common health problem that affects 25% of the adult population in industrialized societies, and is a major risk factor for myocardial infarction and stroke. However, the pathogenesis of hypertension, as well as the basic mechanisms of blood-pressure control, are insufficiently understood. Although the development of hypertension is complex, involving many different mechanisms, including dysregulation of the autonomic nervous system, renal function, and the balance between water and electrolytes, and increased vascular tone and the resulting rise in peripheral vascular resistance are major determinants of the elevated arterial pressure in hypertension. Since the discovery of the essential role of RhoA and its downstream target, Rho kinase, in the regulation of vascular tone, as well as the antihypertensive effect of a Rho kinase inhibitor, much evidence has accumulated to implicate activation of Rho family proteins in the pathogenesis of hypertension. RhoA remains the most-analyzed member of the Rho proteins in the context of vascular physiology and hypertension, but evidence is accumulating that also points to a role of Rac1 in arterial pathophysiology. In this Review, we discuss progress in our understanding of the role of Rho proteins and their regulators in the pathogenesis of high blood pressure.