Vascular consequences of sympathetic neural activation in obesity

肥胖和高血压之间的联系的机制尚不清楚，但增加的交感神经驱动骨骼肌循环和肾脏已被牵连。这一认识来自交感神经活动和区域去甲肾上腺素周转的直接神经内记录。 已经假设交感神经活动（SNA）的增加直接转化为交感血管收缩张力的升高，但是这些假设尚未被严格地检验。 我们最近获得的初步数据，使用最大的α-肾上腺素能受体阻断前臂血管，表明没有增加交感神经血管紧张度在血压正常的肥胖人群，尽管增加肌肉SNA。 这表明交感神经流出之间存在分离， 和交感神经介导的血管收缩张力。有趣的是，我们也有初步数据表明，在肥胖高血压人群中，肌肉SNA增加与交感血管收缩张力增加有关。 这表明，高血压的易感性与肥胖相互作用，使SNA的增加表现为交感神经血管张力的增加。 本项目将检验SNA的血管收缩作用在肥胖中减弱但在具有高血压倾向的肥胖人群中保留的假设，具体目标如下：1）高血压、阻塞性睡眠呼吸暂停和内脏肥胖对SNA升高的阻力血管表达有何影响？2)内皮一氧化氮的产生是否是SNA对肥胖患者血管张力影响减弱的原因 与瘦的血压正常的人相比，一氧化氮的调节作用在肥胖的高血压人群中减弱了吗？3)在肥胖的正常血压和高血压患者中，不同的饮食成分对SNA和交感神经介导的血管收缩张力有什么影响？ 将通过显微神经造影术评估交感神经至皮肤和骨骼肌的交通。 将通过皮肤（激光多普勒流量）和骨骼肌（通过近红外血氧测定法测量氧合）对动脉内输注α-肾上腺素能拮抗剂的血管舒张反应评估交感神经血管收缩张力。这些研究应该为肥胖对心血管的影响和肥胖对心血管的影响提供新的见解。 易患肥胖相关高血压的因素。

The mechanisms underlying the association between obesity and hypertension are unclear, but increased sympathetic neural drive to skeletal muscle circulation and kidney has been implicated. This insight has been derived from direct intraneural recordings of sympathetic nerve activity and regional norepinephrine turnover. It has been assumed that the increases in sympathetic nerve activity (SNA) directly translate into elevated sympathetic vasoconstrictor tone, but these assumptions have not been rigorously tested. We have recently obtained preliminary data using maximal alpha-adrenergic receptor blockade of the forearm vasculature that demonstrates no increase in sympathetic vascular tone in normotensive obese humans despite increased muscle SNA. This suggests that there is dissociation between sympathetic neural outflow and sympathetically mediated vasoconstrictor tone. Interestingly, we also have preliminary data indicating that in obese hypertensive humans, increased muscle SNA is associated with increased sympathetic vasoconstrictor tone. This suggests that a predisposition to hypertension interacts with obesity to permit the increased SNA to be expressed as increased sympathetic vascular tone. This project will test the hypothesis that the vasoconstrictor effects of SNA are attenuated in obesity but preserved in obese humans with a predisposition to hypertension, with these specific aims: 1) What are the effects of hypertension, obstructive sleep apnea and visceral adiposity on the resistance vessel expression of elevated SNA? 2) Is endothelial nitric oxide generation responsible for attenuated effects of SNA on vascular tone in obese compared to lean normotensive humans, and is the modulating influence of nitric oxide attenuated in obese hypertensive humans? 3) What are the effects of different dietary components on SNA and sympathetically mediated vasoconstrictor tone in obese normotensive and hypertensive subjects? Sympathetic nerve traffic to skin and skeletal muscle will be assessed by microneurography. Sympathetic vasoconstrictor tone will be assessed by the vasodilator response of skin (laser Doppler flux) and skeletal muscle (oxygenation measured by near infra-red oximetry) to intra-arterial infusion of an alpha-adrenergic antagonist. These studies should provide new insights into the cardiovascular effects of obesity and the factors that predispose to obesity-related hypertension.