INTERACTION OF NA WITH CAPTOPRIL ON VASCULAR A-RESPONSES

NA 与卡托普利对血管 A 反应的相互作用

• 批准号: 3448750
• 负责人: DIANNE C KIKTA
• 金额: $ 6.65万
• 依托单位: GRADUATE HOSPITAL (PHILADELPHIA)
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448750
• 关键词: antihypertensive agents; captopril; cardiovascular pharmacology; dietary mineral; diuretics; nutrient drug interaction; peptidyl dipeptidase A; phenylephrine; vascular smooth muscle

Captopril is an orally active antihypertensive agent, proposed to act primarily, if not solely, by inhibition of angiotensin I converting enzyme. Often though, a low-sodium (Na) diet and/or diuretic must be employed along with captopril in order to completely normalize blood pressure. In addition to lowering pressure, captopril attenuates vascular responses to Alpha-adrenergic agonists and this attenuation is prevented by excess Na-intake. This attenuation of vascular Alpha-adrenergic responsiveness may be an important antihypertensive action of captopril which is often masked by excess dietary Na; therefore, the proposed project is designed to test the hypothesis that Na interacts with captopril on vascular Alpha-adrenergic responses. The effects of both elevtions and reductions in Na concentration on the captopril-induced attenuation of vascular Alpha-adrenergic responsiveness will be tested in rats both acutely, as changes in the intra- and extracellular Na concentration of vascular smooth muscle in vitro, and chronically, as changes in the dietary Na concentration during captopril-treatment for 5-wk. For both studies, Alpha-adrenergic responsiveness will be evaluated as the in vitro responses of rings of both thoracic aorta and caudal artery from rats to the Alpha-adrenergic agonist, phenylephrine. Additional chronic studies will investigate separately the effects of both returning to normal dietary Na and administration of a diuretic to rats fed a high-Na diet on the captopril-induced attentuation of Alpha-adrenergic responses. For this study, Alpha-adrenergic responsiveness will be evaluated as the in vivo pressor responses of unanesthetized, unrestrained rats to phenylephrine and will be measured both prior to (while on high-Na diet) and following return to normal dietary Na or administration of the diuretic for 2 wk. Effects of chronic alterations in dietary Na could be due to either direct effects of the Na itself at the level of vascular smooth muscle or to indirect effects mediated by a variety of possible Na-induced changes, including changes in the plasma levels of a humoral Na-pump inhibitor. The effects of these chronic alterations on vascular Na-pump activity will be evaluated. Results of the acute study should indicate whether Na itself can interact with captopril at the level of vasculr smooth muscle. The proposed studies should provide further insight into how dietary Na and/or diuretics may interact with the antihypertensive action(s) of captopril and help define future studies aimed at investigating the mechanism(s) for this Na/captopril interaction.

卡托普利是一种口服活性降压药，建议用于 主要是抑制血管紧张素转换，如果不是完全的话 酵素。通常情况下，低钠饮食和/或利尿剂必须 与卡托普利一起使用，以使血液完全正常化 压力。除了降低血压外，卡托普利还能减弱血管 对α-肾上腺素能激动剂的反应和这种衰减可通过 钠摄入量过多。血管α-肾上腺素能的这种减弱 反应性可能是卡托普利的重要降压作用 这往往被过量的膳食钠所掩盖；因此，拟议的项目 旨在检验钠与卡托普利相互作用的假设 血管α-肾上腺素能反应。高程和高程的影响 降低钠浓度对卡托普利所致大鼠脑缺血再灌注损伤的影响 将在两只大鼠身上测试血管α-肾上腺素能反应性 急性AS细胞内外Na浓度的变化 血管平滑肌在体外，和慢性一样，在饮食中的变化 卡托普利治疗5wk时的钠浓度。在这两项研究中， α-肾上腺素能反应性将作为体外反应进行评估 从大鼠胸主动脉环和尾动脉环到 肾上腺素能激动剂，苯肾上腺素。更多的慢性研究将 分别研究两者恢复正常膳食钠的影响 以及给喂食高钠饮食的大鼠服用利尿剂 卡托普利引起的α-肾上腺素能反应的注意。为了这个 研究表明，α-肾上腺素能反应性将被评估为体内 非麻醉、自由状态下大鼠对苯肾上腺素和苯肾上腺素的升压反应 将在返回之前(在高钠饮食时)和之后进行测量 至正常膳食钠或给予利尿剂2wk。效应 饮食中钠的慢性变化可能是由于以下两种直接影响之一 对钠本身在血管平滑肌水平上或间接地 由各种可能的钠诱导的变化所介导的效应，包括 一种体液钠泵抑制剂的血浆水平变化。其影响 在这些慢性改变中，血管钠泵活性将是 已评估。急性研究的结果应该表明钠本身 可与卡托普利在血管平滑肌水平上相互作用。这个 拟议的研究应进一步深入了解饮食中的钠和/或 利尿剂可能与卡托普利的降压作用相互作用(S)和 帮助确定未来旨在调查这一机制的研究(S) 钠/卡托普利相互作用。