Showing papers by "Louis J. Ignarro published in 1981"
Journal Article•
1,690 citations
TL;DR: These agents were effective in disaggregating platelets and attenuating aggregation and were associated with a concomitant rise in cigarette smoke, which contains nitric oxide.
621 citations
Journal Article•
TL;DR: Findings are consistent with and strongly support an involvement of cyclic GMP formation in vascular smooth muscle relaxation elicited by nitrogen oxide-containing vasodilators.
Abstract: The purpose of the present study was to determine time course relationship between cyclic GMP accumulation and relaxation in bovine coronary artery and evaluate the effects of recently identified inhibitors, methylene blue and methemoglobin, on these relationships. Arterial strips were suspended in specially mounted tissue baths which permitted continuous recording of isometric tension until rapid freeze-clamping for subsequent determination of cyclic GMP levels by radioimmunoassay. Relaxation and cyclic GMP levels were measured in submaximally contracted strips at zero time (untreated) or 5-sec to 5-min intervals after exposure to 0.5 microliter of nitric oxide, 1 microM glyceryl trinitrate, 1 microM sodium nitroprusside of 1 mM sodium nitrite in the absence or presence of 10 mM methylene blue or 1 microM methemoglobin. Cyclic GMP accumulation preceded onset of relaxation elicited by nitric oxide and glyceryl trinitrate and temporally correlated with relaxation induced by sodium nitroprusside and sodium nitrite. Methylene blue simultaneously inhibited cyclic GMP accumulation and relaxation induced by all four relaxants. In contrast to methylene blue, methemoglobin abolished cyclic GMP accumulation and relaxation elicited by nitric oxide without altering responses to glyceryl trinitrate, sodium nitroprusside and sodium nitrite. These findings are consistent with and strongly support an involvement of cyclic GMP formation in vascular smooth muscle relaxation elicited by nitrogen oxide-containing vasodilators.
542 citations
TL;DR: The hypothesis that nitrates and nitrites relax vascular smooth muscle by stimulating cyclic GMP formation is supported, similar to relaxation and guanylate cyclase activation by nitroso-containing compounds.
Abstract: Relaxation by nitroglycerin, sodium nitrite, and amyl nitrite of bovine coronary arterial smooth muscle was inhibited by the oxidant methylene blue. Methylene blue also inhibited activation of bovi...
325 citations
TL;DR: Observations imply that cysteine, hematin, and their nitrosyl derivatives bind to SH groups at the catalytic site of guanylate cyclase.
71 citations
TL;DR: Data suggest that nitroprusside and nitroglycerin decrease pulmonary vascular resistance by dilating intrapulmonary veins and upstream segments, which is independent of passive factors such as changes in pulmonary blood flow or left atrial pressure and not secondary to an effect of these agents on the systemic circulation.
Abstract: The objective of this study was to determine the direct actions of nitroprusside and nitroglycerin on the pulmonary vascular bed in the intactchest dog. These widely used nitrogen oxide-containing vasodilator agents decreased pulmonary arterial pressure and increased cardiac output without altering left atrial pressure. Reductions in pulmonary arterial pressure and pulmonary vascular resistance were small under resting conditions, but were enhanced when pulmonary vascular tone was elevated by infusion of a stable prostaglandin analog that increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In studies in which pulmonary blood flow to the left lower lobe was maintained constant, nitroprusside and nitroglycerin caused small but significant reductions in lobar arterial and small-vein pressures without significantly affecting left atrial pressure. With constant blood flow, lobar vascular pressures that were reduced in response to the vasodilators were more greatly reduced when lobar vascular resistance was increased by infusion of the prostaglandin analog or serotonin. However, when lobar vascular pressures were elevated by passive obstruction of lobar venous outflow, vasodilator responses to nitroprusside and nitroglycerin were not enhanced. These data suggest that nitroprusside and nitroglycerin decrease pulmonary vascular resistance by dilating intrapulmonary veins and upstream segments. These responses were minimal under control conditions but were enhanced when vascular tone was increased. This vasodilator action is independent of passive factors such as changes in pulmonary blood flow or left atrial pressure and is not secondary to an effect of these agents on the systemic circulation. Pulmonary vasodilator responses to nitroprusside and nitroglycerin were, however, found to be dependent on the existing level of vasomotor tone in the pulmonary vascular bed.
56 citations
TL;DR: Partially purified, heme-free, hepatic soluble guanylate cyclase was activated by NO, S-nitrosocysteine and NO-heme complexes to the extent of 19–34-fold in the presence of 3 mM Mg2+, but only up to 2-fold when the GTP concentration was 1 mM.
36 citations
TL;DR: The data indicate that the effects of these diverse agents on guanylate cyclase activation by preformed NO-heme are similar to their effects on enzyme activation by NO and nitroso compounds, both of which readily form NO- heme complexes.
21 citations
TL;DR: The contractile effects of 5- HT observed in the present study suggest that 5-HT released from platelets could contribute to increased vascular resistance during pulmonary thromboembolism by actively constricting arterial and venous segments of the pulmonary vascular bed in a variety of species, including man.
Abstract: The contractile effects of serotonin (5-hydroxytryptamine, 5-HT) were compared in helical strips of intrapulmonary artery (IPA) and vein (IPV) isolated from lungs of dog, rabbit, cow, and man. 5-HT...
10 citations