[Endothelial dysfunction in peripheral arterial occlusive disease: from basic research to clinical use].
Nitric oxide (NO) exerts pleiotroptic anti-atherosclerotic effects in the vascular wall: vasodilation, inhibition of platelet aggregation, elukocyte adhesion, and smooth muscle cell proliferation. Experimental and clinical studies showed that the biological effects of NO are impaired in patients with peripheral arterial occlusive disease. In a cross over study with 77 PAOD patients, we could demonstrate impaired NO formation by measuring the index metabolites of NO, nitrate and cyclic GMP. One possible mechanism of these pathophysiological changes is accumulation of the endogenous inhibitor of NO synthesis, asymmetrical dimethylarginine (ADMA). The NO-mediated functions of the vascular endothelium will become increasingly important in the clinic: diagnostically, measuring endothelium-dependent vasodilation may become a risk indicator for the development or progression of cardiovascular disease and for assessing the effects of antiatherosclerotic therapy; therapeutically, treatment strategies will be developed aiming at improving endothelial function. In early clinical studies, administration of L-arginine, the amino acid precursor of endogenous NO, has resulted in increased NO formation rates, which may prove therapeutically effective in the future.
Böger
R H
RH
Institut für Klinische Pharmakologie, Medizinische Hochschule Hannover.
Bode-Böger
S M
SM
D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine