Arterial baroreceptor unloading causes hypertension

动脉压力感受器卸载导致高血压

• 批准号: 6832777
• 负责人: TERRY N THRASHER
• 金额: $ 33.41万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832777
• 关键词: baroreceptors; blood pressure; cardiac output; carotid artery; denervation; disease /disorder etiology; dogs; hypertension; telemetry; vascular resistance; baroreceptors; blood pressure; cardiac output; carotid artery; denervation; disease /disorder etiology; dogs; hypertension; telemetry; vascular resistance

DESCRIPTION (provided by the applicant): This application is based on the hypothesis that unloading arterial baroreceptors can cause hypertension. We have developed a model with carotid baroreceptors on one side functional (all other carotid and aortic baroreceptors denervated) in conscious dogs. In this model, ligation of the common carotid artery proximal to the innervated carotid sinus produces a significant and sustained increase in systemic arterial pressure (SAP, 22 +/- 3 mmHg for at least seven days duration, n=6) and plasma renin activity (PRA). Carotid ligation unloads baroreceptors downstream and the reflex increase in SAP returns mean carotid sinus pressure (CSP) to control levels. The cause of the increase in SAP must be related to unloading carotid baroreceptors because removing the ligature on the innervated side after seven days results in a reduction in SAP to control levels. Furthermore, ligation of the common carotid on the denervated side results in a fall in CSP distal to the ligature and does not cause an increase in SAP (n=4). The goal of this application is to elucidate the mechanisms, which drive the hypertension in this model. The aims are first, to extend the observations to include continuous measurements of SAP with the animals in their home cages using telemetry. The second aim is to test the hypothesis that the renal nerves are essential for the maintenance of the hypertension. Carotid baroreceptors will be unloaded as above in dogs with denervated kidneys. The third aim will test the hypothesis that the hypertension is primarily due to an increase in peripheral resistance by measuring cardiac output and pressure simultaneously. The fourth aim will test the hypothesis that increased sympathetic efferent activity is responsible for the hypertension. Control experiments will utilize ligation of the carotid proximal to a denervated carotid sinus. The health implications of this project are startling because current theories disregard participation of baroreceptors in the long-term control of blood pressure. These studies will provide a new framework for understanding the development and maintenance of hypertension.

描述（申请人提供）：此申请基于 假设卸载动脉压力受体会导致高血压。我们 已经在一个侧功能上开发了带有颈动脉压力受体的模型（所有 在有意识的狗中剥离的其他颈动脉和主动脉的压力感受器。在这个 模型，与支配的颈动脉接近颈动脉的连接 鼻窦会产生全身动脉的显着持续增加 压力（SAP，22 +/- 3 mmHg至少持续7天，n = 6）和等离子体 肾素活动（PRA）。颈动力连接卸下压力感受器，下游 SAP回报的反射增加平均颈动脉鼻窦压力（CSP）控制 水平。 SAP增加的原因必须与卸载颈动脉有关 压力感受器是因为在七个后卸下神经支配一侧的绑扎 天数会降低SAP至控制水平。此外，结扎 被取消侧的常见颈动脉导致CSP远端下降 结扎，不会导致SAP增加（n = 4）。目标的目标 应用是为了阐明该机制，以驱动高血压 这个模型。目的是首先扩展观察结果以包括 使用家居笼中的动物对SAP进行连续测量 遥测。第二个目的是检验肾神经是 维持高血压至关重要。颈动作压力感受器会 在带有永恒的肾脏的狗中如上卸下。第三个目标将测试 高血压主要是由于增加 通过同时测量心脏输出和压力，外围电阻。 第四个目标将测试增加交感神经的假设 活动是导致高血压的原因。控制实验将使用 颈动脉近端连接与颈动脉窦。健康 该项目的含义令人震惊，因为当前理论无视 压力感受器参与血压的长期控制。 这些研究将为理解发展提供新的框架 和高血压的维持。