AUTONOMIC FUNCTION IN RENOVASCULAR HYPERTENSION

描述：(改编自应用程序)：脑啡肽抑制释放 自主神经递质的减少，从而降低了对神经刺激的反应。 例如，脑啡肽可以减少迷走神经介导的心动过缓。相反， 肾上腺素能刺激心肌细胞引起脑啡肽升高 制作。高血压患者肾上腺素能刺激增加。这 这使得研究人员推测心脏反应性的降低 高血压患者出现的迷走神经刺激可能与心脏 阿片肽。事实上，初步数据显示心脏脑啡肽升高。 高血压犬的儿茶酚胺含量。调查人员 假设1)高血压引起的交感神经活动增加 减少脑啡肽的降解导致心脏脑啡肽的增加； 2)脑啡肽升高导致自主神经反应性降低 刺激和增加心肌儿茶酚胺含量由于减少 心脏儿茶酚胺释放。实验将在体内进行， 有无慢性仪器化高血压和对照犬 β肾上腺素能受体阻滞剂。心脏脑啡肽降解活性 将在体外进行测量。这些实验旨在回答以下问题： 交感神经活动增加是脑啡肽增加的原因吗？ 心脏脑啡肽是否在体内释放？阿片类药物会抑制心脏功能吗？ 对自主神经刺激的反应？高血压会改变心脏吗？ 前脑啡肽加工或脑啡肽降解？1)压力感受器反射 挑战将在意识清醒的狗身上进行，在发育之前和过程中 肾血管性高血压或假手术。动脉减少 硝普钠的压力刺激交感神经并抑制迷走神经 资金外流。苯肾上腺素升高动脉压抑制交感神经 刺激迷走神经流出。心脏脑啡肽和儿茶酚胺血浆 将测量溢出效应和心血管功能。此外, 溢出效应和心功能将通过直接刺激 麻醉动物在组织前的迷走神经和交感神经 所有组中的集合。阿片肽对压力感受器反射的影响 将通过在现场重复压力反射挑战来测试功能 非选择性阿片受体拮抗剂丁丙诺啡。3) 组织脑啡素酶活性、脑啡肽原产物和 将制作高血压与假对照组动物的儿茶酚胺含量。 心脏的特异性将通过检查其他组织(肾上腺)来确定 腺、肾、肺、骨骼肌)。高血压仍然是一个严重的问题 人群中的心血管问题。有人建议，这一结果 将促进知识，并可能改善阿片类药物的治疗使用 心脏病理的患者。

DESCRIPTION: (Adapted from the application): Enkephalins inhibit release of autonomic transmitters, thus, decreasing responses to nerve stimulation. For instance, enkephalins reduce vagally-mediated bradycardia. Conversely, adrenergic stimulation to cardiomyocytes causes increased enkephalin production. Increased adrenergic stimulation is seen in hypertension. This led the investigators to speculate that the decreased cardiac responsiveness to vagal nerve stimulation seen in hypertension may be linked to cardiac opioid peptides. Indeed, preliminary data show increased cardiac enkephalin and catecholamine content in hypertensive dogs. The investigators hypothesize that 1) hypertension-induced increases in sympathetic activity decrease enkephalin degradation leading to increased cardiac enkephalins; and 2) increased enkephalins cause decreased responsiveness to autonomic stimulation and increased cardiac catecholamine content due to decreased cardiac catecholamine release. Experiments will be conducted in vivo with chronically instrumented hypertensive and control dogs with and without beta-adrenergic receptor blockade. Cardiac enkephalin degrading activity will be measured in vitro. The experiments are designed to answer: Are increases in sympathetic activity responsible for increased enkephalins? Are cardiac enkephalins released in vivo? Do opioids depress cardiac responses to autonomic stimulation? Does hypertension change cardiac proenkephalin processing or enkephalin degradation? 1) Baroreflex challenges will be performed in conscious dogs before and during development of renovascular hypertension or the sham procedure. Decreased arterial pressure by nitroprusside stimulates sympathetic and depresses vagal outflows. Increased arterial pressure by phenylephrine inhibits sympathetic and stimulates vagal outflows. Cardiac enkephalin and catecholamine plasma spillover and cardiovascular function will be measured. In addition, spillover and cardiac function will be measured with direct stimulation of the vagus and sympathetic nerves in anesthetized animals before tissue collection in all groups. 2) Opioid peptide influence on baroreflex function will be tested by repeating baroreflex challenges in the presence of the non-selective opioid receptor antagonist, diprenorphine. 3) Measurement of tissue enkephalinase activity, proenkephalin products and catecholamine content in hypertensive vs. sham control animals will be made. Cardiac specificity will be determined by examining other tissues (adrenal gland, kidney, lung, skeletal muscle). Hypertension remains a serious cardiovascular problem in the population. It is suggested that the results will advance knowledge and may improve therapeutic use of opiates in patients with cardiac pathology.