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 NG-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 < .001). Short-term smoking (n = 11) increased blood pressure, heart rate, and plasma epinephrine concentrations (P < .05 or less); enhanced endothelin-1-induced vasoconstriction (delta FVR, 457 +/- 192% versus 254 +/- 143%, P < .01); and decreased norepinephrine-induced vasoconstriction (P < .05), but had no effect on the other interventions. CONCLUSIONS Long-term smoking is associated with a diminished nitric oxide-dependent component of basal vascular tone and an impaired endothelium-dependent vasodilator response to low-dose endothelin-1 and short-term smoking enhances endothelin-1-induced vasoconstriction. Impaired endothelial control of vascular tone might reflect impairment of normal antiatherosclerotic endothelial functions in smokers, but the relevance of smoking-induced enhancement of endothelin-1 vasoconstriction remains to be determined.

Endothelin-1 and Vascular Tone in Subjects With Atherogenic Risk Factors

“…15,16 However, others have shown that smoking is associated with an acute but transient elevation in ET-1 levels 40 and that only acute, but not chronic, exposure to cigarettes results in an exaggerated vasoconstrictive response to exogenous ET-1 relative to controls. 41 The lack of significant vasodilation with BQ-123 in this study suggests that, compared with hypertension, ET-1 does not contribute substantially to vascular tone in smokers, especially via the ET A receptor. All of the smokers in this study were considered heavy smokers, because they consumed between 10 and 30 cigarettes/d.…”

Smoking and choroidal thickness in patients over 65 with early-atrophic age-related macular degeneration and normals

“…41 Smoking appears to impair endothelial cell function in many vascular regions, and evidence supports long-term vasoconstriction and altered endothelial response 37,42,43 to various vasoactive mediators in tobacco smoke. 40,44,45 Human studies indicate abnormal choroidal vascular reactivity to carbogen (high oxygen) inhalation in chronic smokers. 30 Substances in cigarette smoke have additionally been demonstrated to induce direct oxidative damage to endothelium.…”

Effects of l -Arginine on Atherogenesis and Endothelial Dysfunction due to Secondhand Smoke

“…22 Active tobacco smokers exhibit abnormal vascular reactivity that may contribute to the pathogenesis of smoking-induced cardiovascular disease. Active smoking reduces basal NO release 23 and impairs NO mediated endothelium-dependent relaxation of the forearm 24 and coronary 25 vasculature. Active smoking also causes abnormal constrictor responses in the coronary vasculature.…”