Abstract
A high amount of salt in the diet increases blood pressure (BP) and leads to salt-sensitive hypertension in individuals with impaired renal sodium excretion. Small guanosine triphosphatase (GTP)ase Rho and Rac, activated by salt intake, play important roles in the pathogenesis of salt-sensitive hypertension as key switches of intracellular signaling. Focusing on Rho, high salt intake in the central nervous system increases sodium concentrations of cerebrospinal fluid in salt-sensitive subjects via Rho/Rho kinase and renin-angiotensin system activation and causes increased brain salt sensitivity and sympathetic nerve outflow in BP control centers. In vascular smooth muscle cells, Rho-guanine nucleotide exchange factors and Rho determine sensitivity to vasoconstrictors such as angiotensin II (Ang II), and facilitate vasoconstriction via G-protein and Wnt pathways, leading to increased vascular resistance, including in the renal arteries, in salt-sensitive subjects with high salt intake. In the vascular endothelium, Rho/Rho kinase inhibits nitric oxide (NO) production and function, and high salt amounts further augment Rho activity via asymmetric dimethylarginine, an endogenous inhibitor of NO synthetase, causing aberrant relaxation and increased vascular tone. Rho-associated mechanisms are deeply involved in the development of salt-sensitive hypertension, and their further elucidation can help in developing effective protection and new therapies.
Highlights
Hypertension is the most important risk factor for stroke, heart disease, and kidney disease, with serious implications for life expectancy and disability [1]
Small GTPases Rho and Rac, which are activated by dietary salt intake, play important roles in the pathogenesis of salt-sensitive hypertension through various mechanisms as key switches of intracellular signaling
They are involved in vasoconstriction via the G-protein and Wnt pathways regulating myosin light chains (MLCs) phosphorylation in contractile machinery, leading to increased renal vascular resistance and decreased renal blood flow (RBF)
Summary
Hypertension is the most important risk factor for stroke, heart disease, and kidney disease, with serious implications for life expectancy and disability [1]. There is a promotion of aldosterone-releasing factor production in adipocytes [26,27,28,29], resulting in hyperaldosteronism that is not completely suppressed by salt intake [25], abnormally enhanced RAAS, and SNS activation [20,30], which enhances renal sodium reabsorption and leads to salt-sensitive hypertension. The activation of the RhoA/ROCK pathway plays a pivotal role in the pathogenesis of hypertension and cardiovascular-renal diseases through interaction with Ang II, oxidative stress, and nitric oxide (NO) [49,50] Both Rac and Rho, belonging to the same Rho family, are small proteins, they deeply implicate the mechanism of salt-sensitive hypertension. We focus on the role of Rho in the pathogenesis of salt-sensitive hypertension, with occasional contrast to that of Rac
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
