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(Hypertension. 2003;41:1106.)
© 2003 American Heart Association, Inc.

Scientific Contributions

PDE5 Inhibitor Sildenafil Citrate Augments Endothelium-Dependent Vasodilation in Smokers

Masashi Kimura; Yukihito Higashi; Keiko Hara; Kensuke Noma; Satoshi Sasaki; Keigo Nakagawa; Chikara Goto; Tetsuya Oshima; Masao Yoshizumi; Kazuaki Chayama

From the Department of Medicine and Molecular Science (M.K., K.No., S.S., K.Na., K.C.), Department of Cardiovascular Physiology and Medicine (Y.H., M.Y.), Division of Physical Therapy, Institute of Health Sciences (C.G.), and Department of Clinical Laboratory Medicine (T.O.), Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

Correspondence to Dr Yukihito Higashi, Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Mimami-ku, Hiroshima 734-8551, Japan. E-mail yhigashi{at}hiroshima-u.ac.jp

Smoking is associated with endothelial dysfunction. The purpose of this study was to determine the effect of sildenafil, an inhibitor of phosphodiesterase type 5 (PDE5), on endothelial function in smokers. We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after oral sildenafil administration (100 mg) with a strain-gauge plethysmograph in 10 young healthy male smokers and 10 young healthy male nonsmokers. FBF response to ACh was lower in smokers than in nonsmokers. The vasodilatory effects of SNP were similar in both groups. Sildenafil increased the FBF response to ACh from 9.3±2.0 to 12.5±3.5 mL/min per 100 mL tissue in smokers and from 12.6±5.6 to 19.6±8.4 mL/min per 100 mL tissue in nonsmokers, and it increased the response to SNP from 13.3±3.9 to 15.1±4.3 mL/min per 100 mL tissue in smokers and from 14.8±5.2 to 18.4±6.0 mL/min/100 mL tissue in nonsmokers (P<0.05 for all). The ratio of maximal ACh-stimulated FBF expressed as a ratio of maximal SNP-stimulated FBF significantly increased after administration of sildenafil in both groups. Infusion of N^G-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished sildenafil-induced augmentation of the FBF response to ACh in both groups. The findings suggest that endothelial function is impaired in smokers compared with that in nonsmokers, that inhibition of PDE5 by sildenafil significantly increases nitric oxide-mediated vasodilation, and that the activities of PDE5 in smokers and nonsmokers may be similar.

Key Words: nitric oxide synthase • smoking • endothelium • blood flow • acetylcholine • vasodilation

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