Lisinopril improves endothelial function in chronic cigarette smokers

Cigarette smoking is a pernicious risk factor for the pathogenesis of coron ary artery disease, and endothelial dysfunction is an important antecedent event in this process. This is important, as cigarette smoke is directly to xic to endothelial cells. Inhibitors of angiotensin-converting enzyme (ACE) have been shown to improve endothelial function in diabetes and hyperchole sterolaemia, and are a promising option in smokers. We treated 23 subjects (age 38 +/- 12 years; mean +/-S.D.) for 8 weeks with 20 mg of lisinopril in a randomized controlled trial. Endothelial function was assessed by measur ement of forearm blood flow responses to intraarterial infusions of endothe lial-dependent and -independent vasodilators and an endothelial-dependent v asoconstrictor [acetylcholine, sodium nitroprusside and monomethyl-L-argini ne (L-NMMA) respectively] using venous occlusion plethysmography. Lisinopri l significantly increased the forearm blood flow response to acetylcholine by 20% [lisinopril, 3.12 +/- 0.37 (mean +/- S.E.M.); placebo, 2.58 +/- 0.25 ; P = 0.02. 95% confidence intervals (CI) 0.09, 1.06] (values given are rat ios of flow in the infused arm to that in the control arm); there was no ef fect on the response to sod i um nitroprusside (lisinopril, 3.97 +/- 0.40; placebo, 3.92 +/- 0.39; P = 0.84; 95% CI -0.50, 0.61). The vasoconstrictor response to L-NMMA demonstrated a significant improvement (lisinopril, 0.77 +/- 0.06; placebo, 0.95 +/- 0.05; P < 0.01; 95% CI -0.09, -0.27). In concl usion, these results indicate that ACE inhibition can improve endothelial f unction in cigarette smokers. We show that lisinopril improves both recepto r-mediated and tonic NO release. The mechanism could be either that lisinop ril limits the angiotensin Ii-induced production of superoxide radicals whi ch would normally inactivate NO, or that lisinopril may increase bradykinin -mediated NO release.