Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
Department of Kinesiology, University of Wisconsin, Madison, Wisconsin.
Am J Physiol Heart Circ Physiol. 2022 Jan 1;322(1):H25-H35. doi: 10.1152/ajpheart.00449.2021. Epub 2021 Nov 5.
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 with 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. 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 (ΔFVC) was quantified during graded brachial artery infusion of isoproterenol (Iso, 1-12 ng/100 g/min) in normal weight ( = 36) and adults with obesity ( = 22) (18-40 yr old). In a subset of participants, Iso-mediated vasodilation was examined before and during inhibition of NOS [-monomethyl-l-arginine (l-NMMA)], COX (ketorolac), and NOS + COX (l-NMMA + ketorolac). Iso-mediated increases in FVC did not differ between groups ( = 0.57). l-NMMA attenuated Iso-mediated ΔFVC in normal weight ( = 0.03) but not adults with obesity ( = 0.27). In normal weight adults, ketorolac increased Iso-mediated ΔFVC ( < 0.01) and this response was lost with concurrent l-NMMA ( = 0.67). In contrast, neither ketorolac ( = 0.81) nor ketorolac + l-NMMA ( = 0.40) altered Iso-mediated ΔFVC in adults with obesity. Despite shifts in COX and NOS, β-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. We examined β-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, β-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.
中心性肥胖与血压的交感神经支持增加有关。β-肾上腺素能受体 (β-AR) 缓冲交感神经介导的血管收缩，肥胖的临床前模型中 β-AR 介导的血管舒张减弱。有了这些信息，我们假设与正常体重成年人相比，肥胖者的 β-AR 血管舒张会更低。由于正常体重成年人的 β-AR 血管舒张受环氧化酶 (COX) 对一氧化氮合酶 (NOS) 的限制，因此我们进一步探讨了 COX 和 NOS 对该队列中 β-AR 血管舒张的贡献。通过多普勒超声测量前臂血流量 (FBF) 和平均动脉血压 (MAP，肱动脉导管)，并计算前臂血管传导率 (FVC) (FVC = FBF/MAP)。在正常体重者 (= 36)和肥胖者 (= 22) (18-40 岁) 中，在分级肱动脉输注异丙肾上腺素 (Iso，1-12 ng/100 g/min) 期间，从基线 (ΔFVC) 定量测量 FVC 的升高。在一部分参与者中，在抑制 NOS[-单甲基-l-精氨酸 (l-NMMA)]、COX(酮咯酸)和 NOS+COX(l-NMMA+酮咯酸)之前和期间检查了 Iso 介导的血管舒张。两组之间的 Iso 介导的 FVC 增加没有差异 ( = 0.57)。l-NMMA 减弱了正常体重者的 Iso 介导的 ΔFVC ( = 0.03)，但对肥胖者没有影响 ( = 0.27)。在正常体重成年人中，酮咯酸增加了 Iso 介导的 ΔFVC (<0.01)，而同时抑制 l-NMMA 则消除了这种反应 ( = 0.67)。相比之下，酮咯酸 ( = 0.81) 或酮咯酸 + l-NMMA ( = 0.40) 均未改变肥胖者的 Iso 介导的 ΔFVC。尽管 COX 和 NOS 发生了变化，但肥胖的年轻成年人的 β-AR 血管舒张仍然存在。这些数据突出了肥胖的年轻人类中微血管控制机制存在代偿性变化。我们检查了肥胖和正常体重人类骨骼肌中的β-肾上腺素能受体介导的血管舒张。结果表明，尽管环氧化酶和一氧化氮合酶的贡献发生了变化，但肥胖的年轻健康成年人的 β-肾上腺素能介导的血管舒张相对保留。这些数据突出了肥胖过程早期微血管控制机制的亚临床变化，并表明肥胖持续时间和/或原发性衰老的增加可能导致明显的功能障碍。
