(Circulation. 1999;99:491-497.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
L-Arginine Normalizes Coronary Vasomotion in Long-Term Smokers
From the Department of Molecular and Medical Pharmacology, UCLA School of Medicine, and Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles.
Correspondence to Heinrich R. Schelbert, MD, UCLA School of Medicine, 23-120 CHS, Los Angeles, CA 90095-1735. E-mail hschelbert{at}mednet.ucla.edu
Background—Noninvasive measurements of myocardial blood flow (MBF) with PET revealed an abnormal coronary vasomotor response to cold pressor 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 13N-labeled ammonia and PET in 11 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 pressor test. On day 2, MBF was measured during cold pressor 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-1 · 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 pressor 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 pressor test combined with PET imaging may allow the noninvasive identification of coronary endothelial dysfunction in humans.
Key Words: blood flow • smoking • cold pressor test • endothelium • tomography
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