N ‐Acetylcysteine enhances nitroglycerin‐induced headache and cranial arterial responses

The effects of N ‐acetylcysteine, a sulfhydryl group donor, on nitroglycerin‐induced headache and dilation of temporal and radial arteries were investigated in 11 healthy volunteers. Nitroglycerin, 0.06 µg/kg/min, was infused for 20 minutes immediately after and 120 minutes after pretreatment with N ‐acetylcysteine (100 mg/kg) or placebo. Arterial diameters were measured with high frequency ultrasound, and pain was scored by use of a previously evaluated 10‐point scale. Plasma levels of free ( n = 2) and total ( n = 11) N ‐acetylcysteine were determined. N ‐Acetylcysteine potentiated the headache response (median headache score, 3 versus 1), and the headache retained its vascular characteristics. Temporal artery dilation was also potentiated by N ‐acetylcysteine, 139% ± 3% versus 127% ± 3% of baseline, whereas the radial artery was unaffected. The potentiation was most pronounced after the first nitroglycerin infusion (12% versus 4.5% compared with placebo). A prolonged dilation of the temporal artery was observed only after the first nitroglycerin infusion, when high levels of N ‐acetylcysteine were present. Clinical Pharmacology and Therapeutics (1992) 52, 125–133; doi: 10.1038/clpt.1992.121