Preserved β-adrenergic-mediated vasodilation in skeletal muscle of young adults with obesity despite shifts in cyclooxygenase and nitric oxide synthase

Central adiposity is associated with greater sympathetic support of blood pressure. beta-adrenergic receptors (beta-AR) buffer sympathetically mediated vasoconstriction and beta-AR-mediated vasodilation is attenuated in preclinical models of obesity. With this information, we hypothesized beta-AR vasodilation would be lower in obese compared with normal weight adults. Because beta-AR vasodilation in normal weight adults is limited by cyclooxygenase (COX) restraint of nitric oxide synthase (NOS), we further explored the contributions of COX and NOS to beta-AR vasodilation in this cohort. Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured and forearm vascular conductance (FVC) was calculated (FVC = FBF/MAP). The rise in FVC from baseline (Delta FVC) was quantified during graded brachial artery infusion of isoproterenol (Iso, 1-12 ng/100 g/min) in normal weight (n = 36) and adults with obesity (n = 22) (18-40 yr old). In a subset of participants, Iso-mediated vasodilation was examined before and during inhibition of NOS [N-G-monomethyl-L-arginine (L-NMMA)], COX (ketorolac), and NOS - COX (L-NMMA - ketorolac). Iso-mediated increases in FVC did not differ between groups (P = 0.57). L-NMMA attenuated !so-mediated Delta FVC in normal weight (P = 0.03) but not adults with obesity (P = 0.27). In normal weight adults, ketorolac increased !so-mediated Delta FVC (P < 0.01) and this response was lost with concurrent L-NMMA (P = 0.67). In contrast, neither ketorolac (P = 0.81) nor ketorolac L-NMMA (P = 0.40) altered Iso-mediated Delta FVC in adults with obesity. Despite shifts in COX and NOS, beta-AR vasodilation is preserved in young adults with obesity. These data highlight the presence of a compensatory shift in microvascular control mechanisms in younger humans with obesity. NEW & NOTEWORTHY We examined beta-adrenergic receptor-mediated vasodilation in skeletal muscle of humans with obesity and normal weight. Results show that despite shifts in the contribution of cyclooxygenase and nitric oxide synthase, beta-adrenergic-mediated vasodilation is relatively preserved in young, otherwise healthy adults with obesity. These data highlight the presence of subclinical changes in microvascular control mechanisms early in the obesity process and suggest duration of obesity and/or the addition of primary aging may be necessary for overt dysfunction.

Automated summary

Central adiposity is associated with reduced beta-adrenergic receptor-mediated vasodilation in obese individuals compared to normal weight adults. However, in young adults with obesity, beta-adrenergic receptor-mediated vasodilation is relatively preserved despite changes in cyclooxygenase and nitric oxide synthase. This highlights the presence of compensatory mechanisms in microvascular control in obese individuals.