title: Involvement of Rho GTPases and their regulators in the pathogenesis of hypertension.
abstract: Proper regulation of arterial blood pressure is essential to allow permanent adjustment of nutrient and oxygen supply to organs and tissues according to their need. This is achieved through highly coordinated regulation processes controlling vascular resistance through modulation of arterial smooth muscle contraction, cardiac output, and kidney function. Members of the Rho family of small GTPases, in particular RhoA and Rac1, have been identified as key signaling molecules playing important roles in several different steps of these regulatory processes. Here, we review the current state of knowledge regarding the involvement of Rho GTPase signaling in the control of blood pressure and the pathogenesis of hypertension. We describe how knockout models in mouse, genetic, and pharmacological studies in human have been useful to address this question.
authors.affiliation: a INSERM; U1087; l'institut du thorax ; Nantes , France.
authors.forename: Gervaise
authors.initials: G
authors.lastname: Loirand
authors.forename: Pierre
authors.initials: P
authors.lastname: Pacaud
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002490:Central Nervous System / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000473:pathology*; D007668:Kidney / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: AT1 receptor, type 1 Ang II receptor; Ang II, angiotensine II; ENaCs, epithelial Na+ channels; Et-1, endothelin-1; GAPs, GTPase-activating proteins; GEFs, exchange factors; GTPase activating proteins; GTPases; MLC, 20 kDa-myosin light chain; MLCK, MLC kinase; MLCP, MLC phosphatase; NA, noradrenaline; NHE3, sodium-hydrogen exchanger isoform 3.; NO, nitric oxide; NTS, nucleus tractus solitaries; PDE5, type 5 phosphodiesterase; PKG, cGMP-dependent protein kinase; Rock, Rho-kinase; SHR, spontaneously hypertensive rats; SHRSP, stroke-prone SHR; TxA2, thromboxane A2; artery; blood pressure; cardiovascular; eNOS, endothelial NO synthase; exchange factors; signal transduction; small G proteins; smooth muscle; vasoconstriction