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: 3448752
• 负责人: DIANNE C KIKTA
• 金额: $ 7.05万
• 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 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448752
• 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抗高血压药，建议发挥作用 主要（如果不是仅仅）通过抑制血管紧张素 I 转化 酶。 但通常情况下，低钠 (Na) 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。 除降低压力外，卡托普利还可减弱血管 对α-肾上腺素能激动剂的反应，这种减弱是通过 钠摄入过多。 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抗高血压作用 这常常被膳食中过量的钠所掩盖；因此，拟议的项目 旨在检验 Na 与卡托普利相互作用的假设 血管α-肾上腺素能反应。 海拔和高度的影响 Na浓度的降低对卡托普利诱导的减弱 将在大鼠中测试血管α-肾上腺素能反应性 随着细胞内和细胞外 Na 浓度的变化， 血管平滑肌在体外和长期随着饮食的变化 卡托普利治疗 5 周期间的 Na 浓度。 对于这两项研究， α-肾上腺素能反应性将作为体外反应进行评估 大鼠胸主动脉和尾动脉环 α-肾上腺素能激动剂，去氧肾上腺素。 额外的长期研究将 分别研究恢复正常膳食钠的影响 以及对喂食高钠饮食的大鼠施用利尿剂 卡托普利诱导的α-肾上腺素能反应减弱。 为了这 研究中，α-肾上腺素能反应性将被评估为体内 未麻醉、不受约束的大鼠对去氧肾上腺素的升压反应 将在回归之前（高钠饮食期间）和回归之后进行测量 恢复正常膳食钠或服用利尿剂 2 周。 效果 膳食钠的慢性变化可能是由于直接影响 Na本身在血管平滑肌水平或间接 由各种可能的钠引起的变化介导的影响，包括 体液钠泵抑制剂血浆水平的变化。 效果 这些对血管钠泵活性的慢性改变将是 评价。 急性研究的结果应表明Na本身是否 可以在血管平滑肌水平与卡托普利相互作用。 这 拟议的研究应进一步深入了解膳食钠和/或 利尿剂可能与卡托普利的抗高血压作用相互作用 帮助确定旨在调查其机制的未来研究 Na/卡托普利相互作用。