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: 3448751
• 负责人: DIANNE C KIKTA
• 金额: $ 6.72万
• 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/3448751
• 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.

Captopril是一种口服活性抗高血压药，建议采取行动， 主要（如果不是唯一的话）通过抑制血管紧张素I转化 酵素 通常，低钠（Na）饮食和/或利尿剂必须 与卡托普利一起沿着使用，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紧张素转换酶的活性， 对α-肾上腺素能激动剂的反应，这种衰减被阻止， 过量钠摄入 这种血管α-肾上腺素能的衰减 反应性可能是卡托普利的一个重要降压作用 这往往是由过量的膳食钠掩盖;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 这两个海拔的影响， Na浓度降低对卡托普利诱导的 血管α-肾上腺素能反应性将在大鼠中进行测试， 急性，作为内和细胞外钠浓度的变化， 血管平滑肌在体外，并长期，作为饮食的变化， 卡托普利治疗5周期间的钠浓度。 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价 从大鼠胸主动脉和尾动脉环到 α-肾上腺素能激动剂苯肾上腺素。 其他慢性研究将 分别研究恢复正常饮食钠的影响， 以及对高钠饮食的大鼠给予利尿剂， 卡托普利诱导的α-肾上腺素能反应减弱。 为此 在本研究中，α-肾上腺素能反应性将作为体内 未麻醉、不受约束的大鼠对苯肾上腺素和 将在返回之前（高钠饮食期间）和返回之后进行测量 正常饮食钠或给予利尿剂2周。 影响 饮食钠的慢性改变可能是由于直接影响 钠本身在血管平滑肌水平或间接 各种可能的钠诱导变化介导的效应，包括 体液钠泵抑制剂的血浆水平的变化。 的影响 血管钠泵活性的这些慢性改变将是 评估。 急性研究的结果应该表明钠本身是否 能在血管平滑肌水平与卡托普利相互作用。 的 拟议的研究应提供进一步的了解如何饮食钠和/或 利尿剂可能与卡托普利的抗高血压作用相互作用， 帮助确定未来的研究，旨在调查这一机制 Na/Captopril相互作用。