Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia.
This review focuses on the role of impaired endothelial function for the development of atherosclerosis in human arterial hypertension and hypercholesterolemia in vivo. Potential mechanisms underlying impaired endothelial function and decreased bioavailability of nitric oxide under these clinical conditions are discussed. It further addresses therapeutic strategies aimed at improving the bioavailability of nitric oxide in these patients. The overall conclusion is that the bioavailability of nitric oxide is probably impaired, not by a single defect, but by various mechanisms affecting nitric oxide synthesis as well as nitric oxide breakdown. In both diseases increased superoxide anion production and oxidative stress represent a major mechanism. Decreased bioavailability of nitric oxide not only impairs endothelium-dependent vasodilation, but also activates other mechanisms that play an important role in the pathogenesis of atherosclerosis. Thus, therapeutic strategies should aim to restore bioavailability of nitric oxide, which has been demonstrated for lipid-lowering therapy in hypercholesterolemia and blood pressure control in hypertension. In addition, antioxidative strategies will represent a major therapeutic tool against atherosclerotic diseases in the future. Statins and blockers of the renin-angiotensin system seem to have such antioxidative effects independent from their effects on lipid profiles or blood pressure control.
John
Stefan
S
Department of Medicine IV, University of Erlangen-Nürnberg,Klinikum Nürnberg-Süd, Breslauerstr 201, 90471 Nürnberg, Germany.
Schmieder
Roland E
RE
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001682:Biological Availability; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000503:physiopathology*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D011379:Prognosis; D014664:Vasodilation / Q000502:physiology
D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP