The role of nitric oxide in hypertension and renal disease progression.
Endothelial nitric oxide synthase (eNOS) serves a number of functions in the vasculature. In response to stimuli such as shear stress or acetylcholine, eNOS catalyses the production of nitric oxide (NO) from L-arginine. The NO diffuses across the endothelium into neighbouring smooth muscle and induces vasodilation. NO also acts locally to prevent platelet and leucocyte aggregation and inhibits vascular smooth muscle cell proliferation. It has been shown that mice lacking eNOS have decreased blood pressure, decreased heart rate and increased plasma renin activity. It has also been reported that NO production was reduced in patients with essential hypertension compared with normotensive individuals. In several animal models of renal disease (subtotal renal ablation, ureteral obstruction and diabetes), the administration of L-arginine, and probably the increase in NO synthesis, reduced the degree of glomerulosclerosis, ameliorated the changes in the tubulointerstitial compartment of the kidney and also decreased the infiltration of the kidney by invading macrophages. In summary, the L-arginine-NO pathway plays an important role in hypertension, renal disease, inflammation and atherosclerosis. This pathway also interacts with the renin-angiotensin system, the eicosanoid pathway, endothelin, cytokines and regulators of inflammation such as NF-kappaB.
Klahr
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Department of Internal Medicine, Barnes-Jewish Hospital (North Campus) at Washington University School of Medicine, St Louis, MO 63110-1092, USA.
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000502:physiology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000503:physiopathology* / Q000517:prevention & control; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D012079:Renal Circulation / Q000502:physiology*
D009569:Nitric Oxide; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III