L-arginine normalizes coronary vasomotion in long-term smokers

Background-Noninvasive measurements of myocardial blood flow (MBF) with PET revealed an abnormal coronary vasomotor response to cold presser test in healthy long-term smokers. If coronary endothelial dysfunction accounted for this abnormality, we hypothesized that it could be reversed by L-arginine as the substrate for NO synthase. Methods and Results-MBF was quantified with N-13-labeled ammonia and PET in II healthy smokers (age, 45+/-10 years; 27+/-10 years of smoking) and in 12 age-matched nonsmokers on 2 separate days. On day 1, MBF was measured at rest and, after intravenous L-arginine, during cold presser test. On day 2, MBF was measured during cold presser test and then at rest during L-arginine. Baseline rate-pressure product (RPP) (6559+/-1590 versus 7144+/-1157 bpmXmm Hg) and MBF (0.65+/-0.14 versus 0.73 +/-0.13 mL . g(-1) . min(-1)) were similar in nonsmokers and smokers. Cold pressor test increased RPP similarly in both groups (53 +/-26% versus 46+/-26%), whereas MBF increased in nonsmokers (to 0.93 +/-0.25 mL . g(-1) . min(-1); P<0.05) but not in smokers (0.80+/-0.16 mL . g(-l) . min(-1)). The percent MBF increase differed between nonsmokers and smokers (44+/-25% versus 11 +/- 14%; P=0.0017). However, after L-arginine, the magnitude of MBF response to cold presser test no longer differed between groups (48+/-36% versus 48+/-28%), whereas RPP again increased similarly in the 2 groups (59+/-30% versus 44+/-16%). L-Arginine had no effect on resting MBF in smokers or nonsmokers. Conclusions-Our findings implicate the coronary endothelium as the major site of the abnormal vasomotor response in long-term smokers. Cold presser test combined with PET imaging may allow the noninvasive identification of coronary endothelial dysfunction in humans.