Vascular tone and blood pressure control during exercise

描述（由申请人提供）：运动期间血压的调节对于确保重要器官和运动骨骼肌的充分灌注至关重要。有人认为，由于运动期间绝大多数心输出量是针对活动骨骼肌的，因此运动骨骼肌中的血管收缩在维持血压方面是首要的。实际上，申请人的先前出版物证明了即使在重负荷下，在锻炼骨骼肌中也存在大量α肾上腺素能受体介导的血管收缩。刺激血管平滑肌中的非肾上腺素能受体，如嘌呤能（P2X）、神经肽Y（NPY Y1）和内皮素（ETA）受体，也可在静息骨骼肌的血管系统中产生血管收缩，但这些受体对运动骨骼肌中的强直性血管收缩的贡献在很大程度上仍然未知。本申请的初步数据清楚地证明了运动骨骼肌中P2 X和NPY Y1受体介导的血管收缩的潜力。尽管在活动性骨骼肌中存在交感神经血管收缩，但申请人先前的工作证明，运动在骨骼肌的脉管系统中产生α肾上腺素能受体反应性的衰减。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受体反应性在运动期间也减弱，但血管平滑肌中的非肾上腺素能受体是否表现出从休息到运动的类似降低的反应性仍有待确定。支持这一提议的总体假设是，非肾上腺素能受体有助于运动骨骼肌中的血管收缩。提出了两个具体目标：1。目的探讨非肾上腺素能受体在运动性骨骼肌血管收缩中的作用。2.目的：研究静息和运动状态下骨骼肌血管系统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将激动剂和拮抗剂递送到离散的血管床而不改变其他血管床中的动脉压或血流。拟议的研究将提供有价值的新的信息有关的生理机制，血液流动到活跃的骨骼肌在动态运动过程中进行调节。这是一个具有根本重要性的问题，可能对外周血管疾病患者产生重要影响。

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.