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[自发性高血压大鼠中血管紧张素转换酶抑制血管紧张素I时的肾组织血管紧张素]

[Renal tissue angiotensins during converting enzyme inhibition of angiotensin I in spontaneously hypertensive rat].

作者信息

Ingert C, Grima M, Michel B, Barthelmebs M, Imbs J L

机构信息

Institut de pharmacologie et de médecine expérimentale, faculté de médecine, université Louis-Pasteur, Strasbourg.

出版信息

Arch Mal Coeur Vaiss. 1997 Aug;90(8):1135-41.

PMID:9404423
Abstract

To compare the effects of an angiotensin-converting enzyme inhibitor on circulating and tissue renin-angiotensin system, we measured different renin-angiotensin system parameters during the first day of treatment (Day 1) as well as after two weeks of treatment (Day 14). Ramipril was given orally once daily to adult male spontaneously hypertensive rats. Renin activity, angiotensin-converting enzyme activity and levels of angiotensin I and angiotensin II in the plasma, renal cortex and renal medullar were assessed at Day 1 and Day 14 of the treatment. In the plasma, both renin activity and angiotensin I increased 10 to 15 fold one to four hours after acute as well as at Day 14 of ramipril treatment and then returned to basal values within 24 hours. Plasma angiotensin II levels were not significantly decreased at Day 1 or Day 14. The decrease in the angiotensin II/angiotensin I ratio suggested a sustained inhibition of plasma angiotensin-converting enzyme at Day 14. In the renal cortex and medulla, a clearly different pattern was observed: in ramipril treated rats, renin activity in the renal cortex and medulla did not change at Day 1 but at Day 14 we observed a slight and sustained increase in renin activity. Despite very high basal levels of renin activity, angiotensin I levels in the renal cortex were comparable to those in the plasma. The angiotensin I level increased only one-fold one hour after ramipril intake at Day 1 and Day 14. This suggests that angiotensinogen may have a limiting role in the synthesis of angiotensin I in the kidney. Angiotensin II levels were slightly higher in the renal cortex and medulla than in the plasma suggesting local synthesis of the peptide. In the kidney, angiotensin II levels decreased one and four hours after the acute or prolonged ramipril treatment and the angiotensin II/angiotensin I ratio was reduced at the same time. Our results show that the responses of the plasma and kidney components of the renin-angiotensin system to angiotensin-converting enzyme inhibition are different in the plasma and the kidney suggesting that the circulating and tissue renin-angiotensin system are at least in part independent.

摘要

为比较血管紧张素转换酶抑制剂对循环和组织肾素 - 血管紧张素系统的影响,我们在治疗第一天(第1天)以及治疗两周后(第14天)测量了不同的肾素 - 血管紧张素系统参数。将雷米普利每日一次口服给予成年雄性自发性高血压大鼠。在治疗的第1天和第14天评估血浆、肾皮质和肾髓质中的肾素活性、血管紧张素转换酶活性以及血管紧张素I和血管紧张素II的水平。在血浆中,急性给药后以及雷米普利治疗第14天,肾素活性和血管紧张素I在1至4小时内增加10至15倍,然后在24小时内恢复到基础值。第1天或第14天血浆血管紧张素II水平没有显著降低。血管紧张素II/血管紧张素I比值的降低表明在第14天血浆血管紧张素转换酶受到持续抑制。在肾皮质和髓质中,观察到明显不同的模式:在雷米普利治疗的大鼠中,肾皮质和髓质中的肾素活性在第1天没有变化,但在第14天我们观察到肾素活性有轻微且持续的增加。尽管肾素活性的基础水平非常高,但肾皮质中的血管紧张素I水平与血浆中的相当。在第1天和第14天,雷米普利摄入后1小时血管紧张素I水平仅增加1倍。这表明血管紧张素原可能在肾脏中血管紧张素I的合成中起限制作用。肾皮质和髓质中的血管紧张素II水平略高于血浆,提示该肽的局部合成。在肾脏中,急性或长期雷米普利治疗后1小时和4小时血管紧张素II水平降低,同时血管紧张素II/血管紧张素I比值降低。我们的结果表明,肾素 - 血管紧张素系统的血浆和肾脏成分对血管紧张素转换酶抑制的反应在血浆和肾脏中是不同的,这表明循环和组织肾素 - 血管紧张素系统至少部分是独立的。

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