Coronary Vascular and Antiplatelet Effects of Peroxynitrite in Human Tissues

The present study investigated the interrelationship between nitric oxide and its intermediate degradation product, peroxynitrite, on reactivity of isolated human coronary arteries and washed human platelets. Ninety-one ring segments of human coronary arteries, with minimal intimal proliferation, were isolated from 9 patients who underwent cardiac transplantation. All vessels were pretreated with 5 μM indomethacin and precontracted with 0.5-1 μM prostaglandin F2α. Addition of 0.01-300 μM peroxynitrite produced a rapid and dose-dependent relaxation similar to that observed with isolated canine coronary arteries. The IC50 of peroxynitrite induced relaxation was 3.2 ± 0.3 μM. Superoxide dismutase (SOD, 100 u/ml) enhanced, while hemoglobin (3 μM) inhibited, the observed relaxation and changed the IC50 to 0.5 ± 0.1 μM and 63 ± 9.4 μM, respectively. In washed human platelets, addition of 1-100 μM peroxynitrite by itself did not produce any direct effect on platelets, but resulted in a dose-dependent inhibition ...