Central adiposity is associated with greater sympathetic support of blood pressure. β-adrenergic receptors (β-AR) buffer sympathetically-mediated vasoconstriction and β-AR mediated vasodilation is attenuated in preclinical models of obesity. With this information, we hypothesized β-AR vasodilation would be lower in obese compared to normal weight adults. Because β-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 β-AR vasodilation in this cohort. Methods: Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured and forearm vascular conductance was calculated (FVC=FBF/MAP). The rise in FVC from baseline (ΔFVC) was quantified during graded brachial artery infusion of Isoproterenol (ISO, 1-12 ng/100g/min) in normal weight (n=36) and obese (n=22) adults (18-40 years old). In a subset of participants, ISO-mediated vasodilation was examined prior to and during inhibition of NOS (L-NMMA), COX (Ketorolac), and NOS + COX (L-NMMA + Ketorolac). Results: ISO-mediated increases in FVC did not differ between groups (p=0.57). L-NMMA attenuated ISO-mediated ΔFVC in normal weight (p=0.03) but not obese (p=0.27) adults. In normal weight adults, Ketorolac increased ISO-mediated ΔFVC (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 ΔFVC in obese adults. Conclusion: Despite shifts in COX and NOS, β-AR vasodilation is preserved in young obese adults. These data highlight the presence of a compensatory shift in microvascular control mechanisms in younger obese humans.

中文翻译：

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尽管环氧合酶和一氧化氮合酶发生变化，但仍保留β-肾上腺素能介导的年轻肥胖成人骨骼肌血管舒张

中枢性肥胖与更大的血压交感神经支持有关。β-肾上腺素能受体 (β-AR) 缓冲交感神经介导的血管收缩和 β-AR 介导的血管舒张在肥胖的临床前模型中减弱。有了这些信息，我们假设与正常体重的成年人相比，肥胖的 β-AR 血管舒张会更低。由于正常体重成人的 β-AR 血管舒张受到一氧化氮合酶 (NOS) 的环氧合酶 (COX) 抑制的限制，我们进一步探讨了 COX 和 NOS 在该队列中对 β-AR 血管舒张的贡献。方法：测量前臂血流量（FBF，多普勒超声）和平均动脉血压（MAP，肱动脉导管），计算前臂血管电导（FVC=FBF/MAP）。在正常体重（n=36）和肥胖（n=22）成人（18-40岁）。在一部分参与者中，在抑制 NOS（L-NMMA）、COX（酮咯酸）和 NOS + COX（L-NMMA + Ketorolac）之前和期间检查了 ISO 介导的血管舒张。结果：ISO 介导的 FVC 增加在组间没有差异（p=0.57）。L-NMMA 在正常体重 (p=0.03) 但不是肥胖 (p=0.27) 成人中减弱 ISO 介导的 ΔFVC。在正常体重的成年人中，酮咯酸增加了 ISO 介导的 ΔFVC（p<0.01），而这种反应在同时使用 L-NMMA 时消失（p=0.67）。相比之下，酮咯酸 (p=0.81) 和酮咯酸 + L-NMMA (p=0.40) 均不改变肥胖成人中 ISO 介导的 ΔFVC。结论：尽管 COX 和 NOS 发生了变化，β-AR 血管舒张在年轻肥胖成人中得以保留。这些数据强调了年轻肥胖人群微血管控制机制存在补偿性转变。