Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis

AbstractObjectives. We sought to assess smooth muscle function in adults at risk for atherosclerosis.Background. Previous studies in subjects at risk for atherosclerosis have demonstrated arterial endothelial dysfunction, with reduced vasodilator responses after pharmacologic or physiologic stimulation of endothelial nitric oxide (NO). Most have also shown a slight but nonsignificant impairment of vasodilation in response to exogenous sources of NO, such as nitroglycerin (NTG). We hypothesized that NTG responses might be reduced in a large number of consecutively studied adults at risk for atherosclerosis, independent of any impaired endothelium-dependent responses, consistent with concomitant smooth muscle dysfunction.Methods. Using high resolution ultrasound, the dilator response of the brachial artery to 400 μg of sublingual NTG was measured in 800 asymptomatic subjects. Subjects were also assessed for a history of vascular risk factors, blood pressure, total serum cholesterol and flow-mediated endothelium-dependent dilation (EDD).Results. We studied 317 men and 483 women, 38 ± 17 years old (mean ± SD, range 15 to 76). The mean cholesterol level was 5.2 ± 1.3 mmol/liter, and there were 126 smokers and ex-smokers (16 ± 9 mean pack-years) and 105 diabetic subjects. On univariate analysis, a reduced vasodilator response to NTG was associated with high cholesterol, cigarette smoking, diabetes mellitus, increasing age, male gender, larger vessel size and reduced EDD (p ≤ 0.01 for all). On multivariate analysis, diabetes, larger vessel size and reduced EDD were all independently associated with impaired NTG-related vasodilation (p ≤ 0.001 for all). In the 574 nondiabetic subjects who had never smoked cigarettes, the independent relation between EDD and NTG responses was still observed (r = 0.24, p = 0.01).Conclusions. The vasodilator response to exogenous NO is impaired in asymptomatic subjects with reduced EDD, consistent with smooth muscle dysfunction in adults at risk for atherosclerosis