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CARDIOVASCULAR DETERMINANTS OF CATECHOLAMINE RELEASE

儿茶酚胺释放的心血管决定因素

基本信息

批准号：
3335719
负责人：
GORDON L KAUFFMAN
金额：
$ 23.38万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-09-01 至 1992-11-30
项目状态：
已结题

项目摘要

Evaluation of the role of Prostaglandin E2 (PGE2) delivered systemically as intravenously infused PGE2 and centrally by ventriculo-cisternal perfusion in controlling centrally mediated, Angiotensin II dependent, reflexly excited adrenal medullary catecholamine release in acutely anephric dogs are our goals for the next grant period. In anesthetized, heparinized dogs following acute nephrectomy and placement of adreno-femoral shunts and aortic cannulae we will study the dose responsiveness of intravenous PGE2's ability to restore normal adrenal reflex catecholamine release elicited by acute hemorrhage. With an appropriate sub-systemic threshold dose of PGE2 derived from that data, we then will perfuse ventriculo-cisternal PGE2 in anesthetized acutely anephric dogs with threshold quantities of PGE2 on reflex catecholamine release following hemorrhage. Finally, we will infuse, ventriculo-cisternally, Angiotensin II and PGE2 concomitantly to define the central effect of PGE2 on Angiotensin II responsiveness. Ventriculo-cisternally perfused PGE2 will be evaluated in two different ways; in one set of experiments, I.V. Angiotensin and ventriculo-cisternally perfused PGE2 will both be given and in another set of experiments, PGE2 and Angiotensin II will be given concominantly in the ventriculo-cisternal perfusion circuit. Understanding the neuro-hormonal control reflex catecholamine release is one long-term objective; another related goal is understanding whether or not renal hormones, specifically renin and the Angiotensin II generated under its infuence and PGE2, are needed to support central nervous system reflex activity. Such physiologic insights will, we hope, help us understand disordered central nervous system mechanisms involved in clinical hypertension.

评价前列腺素E2（PGE 2）作为全身给药的静脉输注PGE_2和脑室-脑池灌注在控制中枢介导的，血管紧张素II依赖的，反射性的急性无肾犬肾上腺髓质兴奋性儿茶酚胺释放是我们下一个资助期的目标在麻醉、肝素化犬中急性肾切除术和肾上腺股动脉分流术后，我们将研究静脉注射PGE 2的剂量反应性恢复正常肾上腺反射的能力引起的儿茶酚胺释放急性出血适当的亚系统阈值剂量的PGE 2 从这些数据中得出，我们将灌注脑室-脑池PGE 2，麻醉的急性无肾犬，出血后反射性儿茶酚胺释放。最后我们将脑室-脑池同时输注血管紧张素II和PGE 2，明确PGE 2对血管紧张素II反应性的中枢作用。将在两个不同的实验中评价脑池灌注的PGE 2。方法;在一组实验中，静脉注射血管紧张素和将给予脑室-脑池灌注的PGE 2，在实验中，PGE 2和血管紧张素II将伴随给予，脑室-脑池灌注回路了解神经激素控制反射儿茶酚胺释放是一个长期目标;另一个相关的目标是了解肾激素，特别是在其影响下产生的血管紧张素II和PGE 2，需要支持中枢神经系统的反射活动。这种生理我们希望，这些见解能帮助我们理解中枢神经系统紊乱，系统机制参与临床高血压。