SECRETION AND RENAL EFFECTS OF CARDIAC PEPTIDES

描述：（改编自研究者摘要）高血压 心血管疾病影响大约4000 - 6000万美国人， 被认为是冠状动脉疾病的主要原因， 中风是导致大多数心血管死亡的原因 在这个国家。多年来，很明显， 动脉血压调节与身体密切相关 盐和水的平衡。最近的证据表明，几种肽 来源于心房利钠因子的N-末端部分 (ANF)激素原在调节肾功能方面也有重要作用 功能和动脉血压。目前的长期目标 应用程序是为了更好地了解胜利阵线的作用， ANF激素原肽在调节肾功能、血液 容量和血压。申请人将开展研究， 探讨一氧化氮、内皮素和腺苷在脑缺血再灌注损伤中的作用。 ANF和proANF释放的旁分泌调节。申请人已经表明 先前认为proANF 1-30产生尿钠排泄和低血压 通过尚未定义的机制。他建议调查四个 可能的潜在机制，可能有助于利钠尿 这些肽的特性。这些包括前列腺素合成， 血液动力学、cGMP合成和 血管紧张素-醛固酮系统。最后，申请人 建议开发针对大鼠形式的proANF 1-30的特异性抗体 和31-67中所描述的方法来提供这些肽在大鼠中的精确测量 组织和血浆，并作为拮抗剂，在解剖出 这些肽对利钠/抗高血压的作用 作为生理反应的一部分被激活的机制， 体积膨胀和慢性高血压。

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.