Impaired endothelial function in arterial hypertension and hypercholesterolemia: potential mechanisms and differences.
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 and potential differences in these mechanisms between arterial hypertension and hypercholesterolemia are outlined. It further addresses therapeutic strategies aiming to improve 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 represents a major mechanism. However, potential differences in the underlying mechanisms of superoxide production or nitric oxide synthesis are evident between arterial hypertension and hypercholesterolemia. Decreased bioavailability of nitric oxide does not only impair 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. The mechanisms by which nitric oxide bioavailability can be improved by any drug therapy remain to be elucidated and may provide further insights into the mechanisms that are involved in impaired endothelial function and atherogenesis.
John
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Department of Medicine IV, University of Erlangen-Nürnberg, Klinikum Nürnberg-Süd, Nürnberg, Germany.
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D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001158:Arteries / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000503:physiopathology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism
D000959:Antihypertensive Agents; D000960:Hypolipidemic Agents; D009569:Nitric Oxide