[Endogenous and therapeutic nitrates in healthy and arteriosclerotic blood vessels].
Nitrates belong to the most potent drugs for treatment of angina pectoris. Patients with this disease always show arteriosclerotic changes in their coronary arteries. In arteriosclerotic vessels endothelium-dependent relaxation induced by the endogenous vasodilator nitric oxide (NO) is markedly reduced. This article introduces a theory, whereby NO production is not reduced in arteriosclerotic vessels (in the arteriosclerotic aorta of the rabbit it is even enhanced) but that the activity of superoxide dismutase, which normally metabolizes free oxygen-radicals (O2-) is reduced and that NO is metabolized by accumulating superoxides. It is interesting that only endogenous nitrate (NO) can be metabolized by this pathway, whereas in arteriosclerotic vessels exogenous nitro-vasodilatators remain fully effective. For the clinical use of nitrates it is of particular importance that these exhibit different potencies for epicardial coronary vessels and the myocardial microcirculation. Nitroglycerin causes extensive relaxation in isolated large coronary arteries but has only a limited effect on middle-sized vessels and almost none on arteries in the microcirculation. These differences in efficacy of nitroglycerin in the coronary micro- and macrocirculation is probably due to the inability of microvessels to transform nitroglycerin into active metabolites such as S-nitroso-L-cysteine. Comparing vascular and clinical effects of nitroglycerin (in particular dilatation of coronary vessels) and of adenosine (acting in particular on the coronary microcirculation) discloses the great importance of the aforementioned effects on epicardial coronary vessels for treatment of angina pectoris. In this context a vasodilatating effect on the coronary microcirculation might not only be disadvantageous but could even trigger angina pectoris itself.
Harrison
D G
DG
Department of Internal Medicine, Emory University, Atlanta, GA 30322.
D000818:Animals; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005609:Free Radicals; D006801:Humans; D009566:Nitrates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000493:pharmacokinetics / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D009566:Nitrates; D013481:Superoxides; D009569:Nitric Oxide; D005996:Nitroglycerin
Endogene und therapeutische Nitrate in gesunden und arteriosklerotischen Gefässen.