Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers

Abstract

Background: Smoking is a major risk factor for the development of atherosclerosis. Because endothelial dysfunction may be a marker for future atherosclerosis, we investigated the effects of smoking on endothelium- dependent control of vascular tone. Methods and Results: The effects of brachial arterial infusions of N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide synthesis inhibitor; sodium nitroprusside; endothelin-1; and norepinephrine on forearm blood flow (strain-gauge plethysmography) were compared in 29 long-term smokers and 16 nonsmokers. The acute effects of smoking on systemic hemodynamics, plasma catecholamines, and forearm vascular responses to these compounds were investigated in smokers only. Smokers did not differ from nonsmokers (n=16) regarding the vascular effects of sodium nitroprusside (n=13) or vasoconstriction due to norepinephrine and endothelin-1 (n=16). Low-dose endothelin-1-induced vasodilation, believed to reflect endothelial prostacyclin or nitric oxide release, was absent in smokers (n=16), and their increase of forearm vascular resistance (FVR) after L-NMMA (n=13) was impaired (35.6±27.9% versus 118.8±43.2%, P