Vascular smooth muscle responsiveness to nitric oxide is reduced in healthy adults with increased adiposity

Abstract

Vascular smooth muscle responsiveness to nitric oxide, as assessed by nitroglycerin-induced dilation (NID), is impaired in clinical cardiovascular disease, but its relation to adiposity is unknown. We determined the relation of NID to total and abdominal adiposity in healthy adults varying widely in adiposity. In 224 men and women [age, 18–79 years; body mass index (BMI), 16.4–42.2 kg/m2], we measured NID (brachial artery dilation to 0.4 mg sublingual nitroglycerin), total body adiposity [BMI and percent body fat (percent BF via dual-energy X-ray absorptiometry)], and indexes of abdominal adiposity [waist circumference (WC) and waist-to-hip ratio (WHR)]. In a subgroup ( n = 74), we also measured total abdominal fat (TAF), abdominal visceral fat (AVF), and subcutaneous fat (ASF) using computed tomography. Based on multiple linear regression, NID was negatively related to BMI [part correlation coefficient ( rpart) = −0.19, P = 0.004] and abdominal adiposity (WC, rpart = −0.22; WHR, rpart = −0.19; TAF, rpart = −0.36; AVF, rpart = −0.36; and ASF, rpart = −0.30; all P ≤ 0.009) independent of sex, but only tended to be related to total percent BF ( rpart = −0.12, P = 0.07). In a subgroup of subjects with the highest compared with the lowest amount of AVF, NID was 35% lower ( P = 0.003). Accounting for systolic blood pressure, HDL cholesterol, glucose, insulin resistance, adiponectin, and brachial artery diameter reduced or abolished some of the relations between NID and adiposity. In conclusion, NID is or tends to be negatively associated with measures of total adiposity (BMI and percent BF, respectively) but is consistently and more strongly negatively associated with abdominal adiposity. Adiposity may influence NID in part via other cardiovascular risk factors.