Vascular tone and blood pressure control during exercise

描述（由申请人提供）：运动时血压的调节对保证重要器官的充分灌注和锻炼骨骼肌至关重要。由于运动时的心输出量绝大部分流向活跃的骨骼肌，因此骨骼肌运动时的血管收缩对维持血压至关重要。事实上，申请人以前的出版物表明，即使在繁重的工作负荷下，锻炼骨骼肌时α -肾上腺素能受体介导的血管收缩也是实质性的。刺激血管平滑肌中的非肾上腺素能受体，如嘌呤能受体（P2X）、神经肽Y受体（NPY Y1）和内皮素受体（ETA）受体，也可以在静息骨骼肌的脉管系统中产生血管收缩，但这些受体在骨骼肌运动中对强直性血管收缩的作用在很大程度上仍然未知。本应用的初步数据清楚地证明了P2X和NPY Y1受体介导的骨骼肌血管收缩的潜力。尽管在活跃的骨骼肌中存在交感血管收缩，但申请人先前的工作表明，锻炼会导致骨骼肌血管中α肾上腺素能受体反应性的衰减。血管平滑肌中的非肾上腺素能受体是否表现出类似的从休息到运动的反应性降低还有待确定，尽管本申请中描述的初步研究提供了一个有趣的建议，即骨骼肌中的P2X和NPY Y1受体的反应性在运动期间也会减弱。这一建议的总体假设是，非肾上腺素能受体有助于骨骼肌运动中的血管收缩。提出了两个具体目标：1。确定非肾上腺素能受体对骨骼肌运动血管收缩的作用。2. 目的探讨静息和运动时骨骼肌血管非肾上腺素能受体的反应性。拟议研究的一个主要优势是能够研究有意识的运动动物的基本生理机制。实验方案的一个独特方面是能够在不改变其他血管床的动脉压或血流的情况下将激动剂和拮抗剂输送到离散的血管床。提出的研究将提供有价值的新的生理机制，通过血液流向活跃的骨骼肌是在动态运动中调节的。这是一个具有根本重要性的问题，可能对周围血管疾病患者具有重要意义。

DESCRIPTION (provided by applicant): The regulation of blood pressure during exercise is of paramount importance to ensure adequate perfusion of vital organs and exercising skeletal muscle. It has been argued that because the vast majority of cardiac output during exercise is directed toward active skeletal muscle, vasoconstriction in exercising skeletal muscle is of primary importance in maintaining blood pressure. Indeed, previous publications by the applicant demonstrated substantial alpha adrenergic receptor mediated vasoconstriction in exercising skeletal muscle even at heavy workloads. Stimulation of non-adrenergic receptors in vascular smooth muscle, such as purinergic (P2X), neuropeptide Y (NPY Y1), and endothelin (ETA) receptors can also produce vasoconstriction in the vasculature of resting skeletal muscle, but the contribution of these receptors to tonic vasoconstriction in exercising skeletal muscle remains largely unknown. Preliminary data in this application clearly demonstrate the potential for P2X and NPY Y1 receptor mediated vasoconstriction in exercising skeletal muscle. Despite the existence of sympathetic vasoconstriction in active skeletal muscle, previous work by the applicant demonstrated that exercise produces an attenuation of alpha adrenergic receptor responsiveness in the vasculature of skeletal muscle. It remains to be determined whether non-adrenergic receptors in vascular smooth muscle exhibit a similarly reduced responsiveness from rest to exercise although pilot studies described in this application provide an intriguing suggestion that P2X and NPY Y1 receptor responsiveness in skeletal muscle is also attenuated during exercise. The overall hypothesis underlying this proposal is that non-adrenergic receptors contribute to vasoconstriction in exercising skeletal muscle. Two specific aims are proposed: 1. To determine the contribution of non-adrenergic receptors to vasoconstriction in exercising skeletal muscle. 2. To examine non-adrenergic receptor responsiveness in the vasculature of skeletal muscle at rest and exercise. A major strength of the proposed studies is the ability to study basic physiological mechanisms in conscious, exercising animals. A unique aspect of the experimental protocols is the ability to deliver agonists and antagonists to a discrete vascular bed without altering arterial pressure or blood flow in other vascular beds. The proposed studies will provide valuable new information regarding the physiological mechanisms by which blood flow to active skeletal muscle is regulated during dynamic exercise. This is an issue of fundamental importance that may have important implications for individuals with peripheral vascular disease.