Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, 55455, USA.
J Physiol. 2020 Aug;598(15):3155-3171. doi: 10.1113/JP277602. Epub 2020 Jun 12.
The decerebrate mouse provides a novel working model of the exercise pressor reflex (EPR). The decerebrate mouse model of the EPR is similar to the previously described decerebrate rat model. Studying the EPR in transgenic mouse models can define exact mechanisms of the EPR in health and disease.
The exercise pressor reflex (EPR) is defined by a rise in mean arterial pressure (MAP) and heart rate (HR) in response to exercise and is necessary to match metabolic demand and prevent premature fatigue. While this reflex is readily tested in humans, mechanistic studies are largely infeasible. Here, we have developed a novel murine model of the EPR to allow for mechanistic studies in various mouse models. We observed that ventral root stimulation (VRS) in an anaesthetized mouse causes a depressor response and a reduction in HR. In contrast, the same stimulation in a decerebrate mouse causes a rise in MAP and HR which is abolished by dorsal rhizotomy or by neuromuscular blockade. Moreover, we demonstrate a reduced MAP response to VRS using TRPV1 antagonism or in Trpv1 null mice while the response to passive stretch remains intact. Additionally, we demonstrate that intra-arterial infusion of capsaicin results in a dose-related rise in MAP and HR that is significantly reduced by a selective and potent TRPV1 antagonist or is completely abolished in Trpv1 null mice. These data serve to validate the development of a decerebrate mouse model for the study of cardiovascular responses to exercise and further define the role of the TRPV1 receptor in mediating the EPR. This novel model will allow for extensive study of the EPR in unlimited transgenic and mutant mouse lines, and for an unprecedented exploration of the molecular mechanisms that control cardiovascular responses to exercise in health and disease.
去大脑僵直小鼠为运动升压反射（EPR）提供了一个新颖的工作模型。EPR 的去大脑僵直小鼠模型与先前描述的去大脑僵直大鼠模型相似。在转基因小鼠模型中研究 EPR 可以确定 EPR 在健康和疾病中的精确机制。
运动升压反射（EPR）是指由于运动而导致平均动脉压（MAP）和心率（HR）升高的反射，这对于满足代谢需求和防止过早疲劳是必要的。虽然这种反射在人类中很容易测试，但机制研究在很大程度上是不可行的。在这里，我们开发了一种新的小鼠 EPR 模型，以允许在各种小鼠模型中进行机制研究。我们观察到，在麻醉小鼠中刺激腹根（VRS）会引起降压反应和 HR 降低。相比之下，在去大脑僵直小鼠中进行相同的刺激会导致 MAP 和 HR 升高，而这种升高会被背根切断或神经肌肉阻滞所消除。此外，我们使用 TRPV1 拮抗剂或在 Trpv1 缺失小鼠中证明 VRS 引起的 MAP 反应降低，而对被动拉伸的反应仍然完整。此外，我们证明，动脉内给予辣椒素会导致 MAP 和 HR 呈剂量依赖性升高，而选择性和有效的 TRPV1 拮抗剂会显著降低这种升高，或者在 Trpv1 缺失小鼠中完全消除这种升高。这些数据证明了去大脑僵直小鼠模型的发展可用于研究运动引起的心血管反应，并进一步确定 TRPV1 受体在介导 EPR 中的作用。这种新模型将允许在无限的转基因和突变小鼠系中对 EPR 进行广泛研究，并以前所未有的方式探索控制健康和疾病中运动引起的心血管反应的分子机制。
