Arterial Baroreflex Control of Blood Pressure (Exercise)

描述（由申请人提供）：许多研究表明，血压的动脉压反射（CBR）控制在提供交感神经向与动态运动相关的活跃和不活跃组织床的输出的必要调节中起主要作用。此外，我们还记录了尽管CBR介导的MSNA增加，但训练有素的耐力运动员对低血压的血管收缩反应减少。越来越多的证据表明，交感神经向脉管系统流出的调节作用是由活性组织内释放的代谢副产物调节的，并涉及功能性交感神经解机制。功能性交感神经溶解的一种可能机制是，收缩诱导活性肌肉内的代谢物打开atp敏感钾（KATP）通道，从而部分抑制交感血管收缩。然而，最近有研究表明，在运动过程中，CBR介导的血管收缩在活动肌肉中提供了最大的反射性血管收缩反应。因此，我们假设CBR在休息和运动时对MSNA和骨骼肌血管系统的控制中起着重要作用。此外，我们认为CBR对运动肌肉血管舒缩功能的调节被局部代谢副产物及其与其他血管活性物质和活动组织内血管平滑肌的KATP通道的相互作用所改变。此外，这些CBR控制血管系统的机制可以通过耐力运动训练来调节。为了验证这些假设：我们将使用经典的人类单腿运动方案，比较休息、非运动腿（NEL）和运动腿（EL）之间的颈动脉压力反射功能曲线（BP）、MSNA和腿部血管传导（LVC）。颈动脉反射功能将使用我们完善的建模技术进行评估。比较平均配合、高配合耐力训练运动员与接受格列本脲治疗的NIDDM患者和接受二甲双胍治疗的NIDDM患者在静止状态下，NEL和EL（除MSNA外）中BP、MSNA和LVC的CBR功能曲线。我们期望从这个项目中获得的发现将提供一个全面的理解，包括通过动脉压力反射调节动脉血压的基本机制，以及它对调节人类运动中血流与需氧量匹配的活动肌肉组织和非活动肌肉组织的血管舒缩的影响。这些发现将对非胰岛素依赖型糖尿病（NIDDM）、高血压和心力衰竭患者的护理产生影响。

DESCRIPTION (provided by applicant): A number of investigations have demonstrated that arterial baroreflex (CBR) control of blood pressure has a primary role in providing the necessary regulation of the sympathetic neural outflow to active and inactive tissue beds associated with dynamic exercise. In addition, we have documented a reduced vasoconstrictive response to hypotension of the highly trained endurance athlete despite an augmented CBR mediated increase in MSNA. A growing body of evidence suggests that the regulatory role of sympathetic neural outflow to the vasculature is modulated by metabolic by-products released within the active tissue and involve mechanisms of functional sympatholysis. A suggested mechanism of functional sympatholysis is that contraction induced metabolites within the active muscle open ATP-sensitive potassium (KATP) channels and thereby partially inhibit sympathetic vasoconstriction. However, it has recently been demonstrated that the CBR mediated vasoconstriction within the active muscle provides the greatest reflex vasoconstrictor response to hypotension during exercise. Therefore, we hypothesize that the CBR has a fundamental role in the control of MSNA and skeletal muscle vasculature at rest and during exercise. Furthermore, we contend that the CBR regulation of vasomotor function in exercising muscle is altered by local metabolic by-products and their interaction with other vasoactive substances and the KATP channels of the vascular smooth muscle within the active tissue. In addition, these mechanisms of CBR control of the vasculature are modulated by endurance exercise training. To address these hypotheses: Comparisons of carotid baroreflex function curves of blood pressure (BP), MSNA and leg vascular conductance (LVC) will be made between rest, the non-exercising leg (NEL) and the exercising leg (EL) using the classic one-legged exercise protocol performed by humans. Carotid baroreflex function will be assessed using our well established modeling technique. Comparisons of CBR function curves of BP, MSNA and LVC will be made at rest, in the NEL and the EL (except MSNA) between average fit, high fit endurance trained athletes and NIDDM patients treated with glibenclamide and NIDDM patients treated with Metformin. We anticipate that the findings obtained from this project will provide a comprehensive understanding of the fundamental mechanisms involved in the regulation of arterial blood pressure by the arterial baroreflex and its influence on the regulation of vasomotion in active muscle tissue and inactive muscular tissue in matching blood flow to oxygen demand during exercise in humans. These findings will have implications for the care of patients suffering from non-insulin dependent diabetes mellitus (NIDDM), hypertension and cardiac failure.