EFFECT OF INSULIN ON VASCULAR REGULATION IN VISCERALLY OBESE MEN

肥胖与交感神经活动水平增加有关，这可能导致高血压的发展。 然而，肥胖并不总是导致高血压，并且肥胖个体中交感神经活动水平的增加与高血压的存在无关。 这有力地表明，除了交感神经活动增强外，其他因素也参与了肥胖高血压的发病机制。这项提案的长期目标是探索肥胖和高血压之间的联系。 通常，胰岛素介导的血管舒张可以抵消增加的交感神经血管收缩。 在本申请中，我们测试的假设，胰岛素抵抗的发展加剧了内脏肥胖男性交感神经活动增加的高血压效应。 为了验证这一假设，将解决以下具体目标：具体目标1：与瘦男性相比，内脏肥胖男性在休息时交感神经活动水平更高，交感神经活动对交感神经兴奋刺激的反应增强吗？具体目标二：在内脏性肥胖的男性中，交感神经活动和血管阻力之间的正常关系是否增强，从而有利于过度的血管收缩？具体目标3：在内脏性肥胖的男性中，胰岛素对交感神经血管收缩的正常钝化作用在胰岛素抵抗面前是否减弱了？

Obesity is associated with increased levels of sympathetic nerve activity, which may lead to the development of hypertension. However, obesity does not always result in hypertension, and the increased levels of sympathetic activity in obese individuals do not correlate with the presence of hypertension. This strongly suggests that factors in addition to heightened sympathetic nerve activity are involved in the pathogenesis of hypertension in obesity. The long-term goal of this proposal is to explore the link between obesity and hypertension. Normally, insulin mediated vasodilation can offset increased sympathetic vasoconstriction. In this application, we test the hypothesis that the development of insulin-resistance exacerbates the hypertensive effects of increased sympathetic nerve activity in viscerally obese men. To test this hypothesis, the following specific aims will be addressed: Specific Aim 1: Compared to lean men, do viscerally obese men have higher levels of sympathetic nerve activity at rest and are the sympathetic nerve activity responses to sympathoexcitatory stimuli augmented? Specific Aim 2: In viscerally obese men, is the normal relation between sympathetic nerve activity and vascular resistance augmented to favor excessive vasoconstriction? Specific Aim 3: In viscerally obese men, is the normal blunting of sympathetic vasoconstriction by insulin attenuated in the face of insulin resistance?