Journal Article

The role of Rho protein signaling in hypertension

Loirand, Gervaise, Pacaud, Pierre

2010

Overview

Animal models have generated much evidence to implicate the activation of Rho family proteins in the pathogenesis of hypertension. Pharmacological and genetic studies have indicated that Rho-protein signaling pathways also have a role in the generation of high blood pressure in humans. In this article, Drs. Loirand and Pacaud discuss our current knowledge 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. Key Points Arterial hypertension affects 25% of the adult population in industrialized societies The Rho proteins RhoA and Rac1 participate to the control of blood pressure through multiple mechanisms both in the arterial wall and the central nervous system RhoA activation is involved in the pathogenesis of hypertension in multiple animal models and in humans Inhibition of the RhoA target Rho kinase reduces blood pressure in animal models of hypertension and decreases forearm vascular resistance in patients with essential hypertension Genetic models of disruption of Rho protein signaling display abnormal blood pressure or resistance to hypertensive conditions

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/80/86 / 692/420 / 692/699/75/243 / Cardiac Imaging / Cardiac Surgery / Cardiology / Cellular signal transduction / Endothelium, Vascular - enzymology / Endothelium, Vascular - pathology / Genetic aspects / Humans / Hypertension / Hypertension - enzymology / Hypertension - physiopathology / Hypertension, Pulmonary - enzymology / Hypertension, Pulmonary - physiopathology / Medicine / Medicine & Public Health / Muscle, Smooth, Vascular - enzymology / Muscle, Smooth, Vascular - pathology / Physiological aspects / rac1 GTP-Binding Protein - metabolism / review-article / rho GTP-Binding Proteins - metabolism / Rho(D) immune globulin / rho-Associated Kinases - metabolism / Risk Factors / Signal Transduction - physiology