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Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension

Li, Qiang; Youn, Ji-Youn; Cai, Hua

doi: 10.1097/HJH.0000000000000587
Reviews

Reduced nitric oxide bioavailability contributes to endothelial dysfunction and hypertension. The endothelial isoform of nitric oxide synthase (eNOS) is responsible for the production of nitric oxide within the endothelium. Loss of eNOS cofactor tetrahydrobiopterin to initial increase in oxidative stress leads to uncoupling of eNOS, in which the enzyme produces superoxide anion rather than nitric oxide, further substantiating oxidative stress to induce vascular pathogenesis. The current review focuses on recent advances on the molecular mechanisms and consequences of eNOS dysfunction in hypertension, and potential novel therapeutic strategies restoring eNOS function to treat hypertension.

Divisions of Molecular Medicine and Cardiology, Departments of Anesthesiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA

Correspondence to Hua Cai, MD, PhD, Divisions of Molecular Medicine and Cardiology, Departments of Anesthesiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California Los Angeles, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA. Tel: +1 310 267 2303; fax: +1 310 825 0132; e-mail: hcai@mednet.ucla.edu

Abbreviations: 6R-H4B, sapropterin dihydrochloride; AAA, abdominal aortic aneurysm; ACE, angiotensin-converting enzyme; ADMA, asymmetric dimethylarginine; Ang II, angiotensin II; BAEC, bovine aortic endothelial cell; Cav-1, caveolin-1; cGMP, 3′,5′-cyclic-guanosine monophosphate; CKD, chronic kidney failure; DHFR, dihydrofolate reductase; DOCA, deoxycorticosterone acetate; eNOS, endothelial nitric oxide synthase; FAD, flavin adenine dinucleotide; FMN, flavin mononucleotide; GTPCHI, GTP cyclohydrolase I; H2B, dihydrobiopterin; H4B, tetrahydrobiopterin; iNOS, inducible nitric oxide synthase; NADPH, nicotinamide adenine dinucleotide phosphate; nNOS, neuronal nitric oxide synthase; NOX, NADPH oxidase; PKG, cGMP-dependent protein kinase; SHR, spontaneously hypertensive rat; SPR, sepiapterin reductase

Received 7 October, 2014

Revised 4 March, 2015

Accepted 4 March, 2015

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