Reduced contribution of NOS and CO to beta adrenergic vasodilation in obesity

Research indicates older obese (OB) individuals (>;55 yrs) exhibit impaired endothelial dependent dilation (EDD). However, there is limited information on the effects of obesity on EDD in younger adults (< 40 yrs). We hypothesized that young OB adults would exhibit decreased β‐adrenergic mediated EDD and demonstrate a lower contribution of nitric oxide synthase (NOS) and cyclooxygenase (COX) to vasodilation compared to lean controls. Forearm blood flow (FBF) was measured with Doppler Ultrasound during infusion of Isoproteronol (ISO), into a brachial artery catheter in 7 OB adults (23±2yrs, BMI=38±4) and 11 lean adults (27±2yrs, BMI=23±1). Forearm Vascular Conductance (FVC=FBF/BP) was calculated to normalize for blood pressure. ISO infusion was repeated after combined inhibition of NOS and COX, with L‐NMMA and Ketorolac, respectively. ISO increased FVC similarly in both groups. Combined NOS‐COX inhibition decreased FVC in both groups (p<0.01), but the decrease tended (p=.06) to be larger in lean (−30 ml/min/mmHg) than the OB group (−11 ml/min/mmHg). EDD to ISO is similar in lean and OB groups, however lean adults rely more on NOS and COX for vasodilation than the OB adults. These data suggest young OB adults maintain β‐adrenergic EDD by activating mechanisms largely independent of NOS and COX. Support NIH R01 HL105820.