Smoking activates Rho-kinase in smooth muscle cells of forearm vasculature in humans

Abstract

Previous studies have shown that smoking is strongly associated with atherosclerosis and coronary vascular disease. Rho-kinase plays an important role in various cellular functions associated with atherosclerosis and hypertension. However, there is no information on the relationship between smoking and Rho-kinase activity in humans. The purpose of this study was to determine the Rho-kinase activity in forearm vascular smooth muscle cells (VSMCs) in healthy young male smokers. We evaluated the forearm blood flow (FBF) responses to fasudil (3, 10, and 30 μg/min for 5 minutes), a Rho-kinase inhibitor, or sodium nitroprusside (0.75, 1.5, and 3.0 μg/min for 5 minutes) in current smokers (n=8) and nonsmokers (n=8). FBF was measured with a strain-gauge plethysmograph. The vasodilatory effect of fasudil was significantly greater in smokers than in nonsmokers (14.9±3.5 versus 10.5±3.6 mL/min per 100 mL tissue; P<0.01). The FBF responses to sodium nitroprusside were similar in the 2 groups (34.7±10.4 versus 33.2±10.2 mL/min per 100 mL tissue; P=0.78). These findings suggest that smoking activates Rho-kinase in forearm VSMCs but does not alter the vasodilatory effect induced by exogenous nitric oxide in forearm VSMCs in healthy young men.