SECRETION AND RENAL EFFECTS OF CARDIAC PEPTIDES

描述：(改编自《调查者摘要》)高血压 心血管疾病影响着大约4000-6000万美国人， 被认为是导致冠状动脉疾病的主要因素 中风是心血管疾病死亡的主要原因 在这个国家。在许多年的时间里，很明显的是 动脉血压的调节与身体密切相关 盐和水的平衡。最近的证据表明，几种多肽 来源于心钠素的N-末端部分 (ANF)前激素在调节肾脏方面也起着重要作用 功能和动脉血压。当前的长期目标 应用是为了更好地理解ANF的作用和 心钠素前激素肽在调节肾功能、血液中的作用 容量和血压。申请者将进行研究以 探讨一氧化氮、内皮素和腺苷在血管紧张素转换酶中的作用 旁分泌调节ANF和proANF的释放。申请人已证明 以前，proANF 1-30会产生钠尿和低血压 到目前为止，还没有明确的机制。他提议调查四个 可能与利钠有关的潜在机制 这种多肽的性质。其中包括前列腺素的合成， 血流动力学、cGMP合成及血管活性的变化 肾素-血管紧张素-醛固酮系统。最后，申请者 建议开发针对鼠型proANF 1-30的特异性抗体 和31-67，以提供这些肽在大鼠体内的准确测量 组织和血浆，并作为拮抗剂解剖出 这些多肽在利钠/降压中的作用 作为生理反应的一部分被激活的机制 体量扩张和慢性高血压。

DESCRIPTION: (Adapted from the Investigator's Abstract) Hypertensive cardiovascular disease affects approximately 40-60 million Americans and is thought to be a primary contributor to coronary artery disease and stroke which collectively account for most of the cardiovascular deaths in this country. Over a period of many years it has become apparent that the regulation of arterial blood pressure is intimately linked to body salt and water balance. Recent evidence suggests that several peptides derived from the N-terminal portion of the atrial natriuretic factor (ANF) prohormone also play an important role in regulating kidney function and arterial blood pressure. The long term goals of the present application are to obtain a better understanding of the role of ANF and ANF prohormone peptides in the regulation of kidney function, blood volume and blood pressure. The applicant will carry out studies to investigate the role of nitric oxide, endothelin and adenosine on the paracrine regulation of ANF and proANF release. The applicant has shown previously that proANF 1-30 produces natriuresis and hypotension through, as yet, undefined mechanisms. He proposes to investigate four likely potential mechanisms that may contribute to the natriuretic properties of this peptide. These include prostaglandin synthesis, alterations in hemodynamics, cGMP synthesis and changes in activity of the renin-angiotensin-aldosterone system. Finally, the applicant proposes to develop specific antibodies to the rat forms of proANF 1-30 and 31-67 to provide accurate measurements of these peptides in rat tissues and plasma and to employ as antagonists in dissecting out the contribution of these peptides to natriuretic/anti-hypertensive mechanisms which are activated as part of the physiological response to volume expansion and chronic hypertension.