Potentiation of the cardiovascular effects of nitroglycerin by N-acetylcysteine.
The biochemical basis of the mechanism of vasodilatation by nitroglycerin (NTG) has not been previously investigated in man. However, evidence from in vitro studies suggests that NTG induces activation of guanylate cyclase via a series of enzymatic reactions that are modulated by the availability of sulfhydryl groups. Cysteine appears to be particularly effective in potentiating guanylate cyclase activation by NTG. To determine whether hemodynamic responsiveness to NTG in man might be modulated by sulfhydryl availability, concentration-response curves for effects of intravenously infused NTG on mean arterial pressure (MAP) and mean pulmonary capillary wedge pressure (PCW) were obtained in 10 patients undergoing cardiac catheterization for investigation of chest pain. NTG infusion was repeated 10 min after the intravenous infusion of 100 mg/kg of the cysteine source N-acetylcysteine (NAC). NAC induced no significant hemodynamic effect, but after NAC infusion there was a significant reduction both in the NTG infusion rate associated with a 10% fall from control values in MAP (25.8 +/- 8.3 to 9.3 +/- 2.7 micrograms/min; p less than .01) and in the infusion rate inducing a 30% reduction in PCW (13.6 +/- 4.6 to 4.2 +/- 1.6 micrograms/min; p less than .02). In a control group of five patients who received no NAC, there was no significant change in responsiveness to NTG between infusions. It is concluded that NAC potentiates the vasodilator effects of NTG in man. This suggests that sulfhydryl availability and/or redox state may be determinants of in vivo responsiveness to NTG.
D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D006328:Cardiac Catheterization; D004357:Drug Synergism; D004789:Enzyme Activation; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D014665:Vasodilator Agents; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D000111:Acetylcysteine