VASOPRESSIN & ALPHA-ADRENOCEPTORS--ELDERLY HYPERTENSION

加压素

• 批准号: 3354017
• 负责人: HARALAMBOS GAVRAS GAVRAS
• 金额: $ 12.13万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-30 至 1991-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354017
• 关键词: aging; alpha adrenergic receptor; alpha antiadrenergic agent; angiotensin /renin /aldosterone hypertension; arginine vasopressin; blood chemistry; cardiovascular pharmacology; clonidine; dietary mineral; diuretics; hormone inhibitor; hormone receptor; human old age (65+); human subject; hypertension; hyponatremia; neurogenic hypertension; platelets; vasoconstrictors

These studies are designed to investigate the contributions and interaction of two vasopressor systems i.e. vasopressin and the sympathetic nervous system in the maintenance of hypertension in the elderly (the thrid major pressor system, renin-angiotensin, having been shown to be suppressed in the elderly). In previous experimental studies we have found evidence suggesting that sodium may prompte high blood pressure by altering the characteristics of alpha2-adrenoceptors, and that the pressor effectiveness of vasopressin is greatly enhanced when the sympathetic system is impaired. In the present proposal we plan to establish the hormonal and alpha2-adrenoceptor profiles (from platelets) in young and old hypertensive and normotensive subjects, to separate alterations associated with hypertension from those attributable to normal aging. We also plan to conduct in elderly hypertensives inpatient metabolic studies to determine the possible pressor contributions of vasopressin (as assessed by blood pressure responses to a V1 inhibitor) after salt loading or sympathetic inhibiton (by clonidine or prazosin) and to test the effect of salt-loading on alpha2-adrenoceptors of salt-sensitive and salt-resistant hypertensives. Finally, we propose to test the therapeutic effect of a vasopressin inhibitor with combined V1 and V2 action in elderly hypertensives with diuretic-induced hyponatremia. These studies should advance our understanding of the mechanisms participating in the maintenance of the non-renin-dependent hypertension in the elderly. They may also provide information leading to new therapeutic approaches suitable for this type of hypertension as well as for the prevention or reversal of certain diuretic-induced complications.

这些研究旨在研究贡献和相互作用 两个加压剂系统，即加压素和交感神经 维持老年人高血压的系统 训练系统，肾素 - 血管紧张素，已被证明已被抑制 老人）。 在先前的实验研究中，我们发现了证据 表明钠可能通过改变 α2-肾上腺素受体的特征，施加功效 当交感神经系统是，加压素的增强 受损。 在本提案中，我们计划建立荷尔蒙和 年轻人和老年高血压 和正常的主题，以分开与 从归因于正常衰老的高血压。 我们还计划 老年高血压住院代谢研究中的行为以确定 加压素的可能施加贡献（如血液评估 盐负荷或交感神经后对V1抑制剂的压力响应） 抑制剂（通过可乐定或prazosin）并测试盐载的作用 对盐敏感和耐盐的α2-肾上腺素受体 高血压。 最后，我们建议测试A的治疗作用 血管加压素抑制剂具有V1和V2的联合作用 利尿剂诱导的低钠血症。 这些研究应该 促进我们对参与机制的理解 维持老年人中非肾素依赖性高血压。 他们 还可以提供信息，从而提供新的治疗方法 对于这种高血压以及预防或逆转 某些利尿剂引起的并发症。