慢性心肌梗死后大鼠体内血管紧张素II、缓激肽和前列腺素对转换酶抑制肾效应的相对贡献。

Relative contribution of angiotensin II, bradykinin, and prostaglandins to the renal effects of converting enzyme inhibition in rats after chronic myocardial infarction.

作者信息

Deck C C, Gaballa M A, Raya T E

机构信息

Department of Internal Medicine, Department of Veterans Affairs Medical Center, Tucson, Arizona, USA.

出版信息

J Cardiovasc Pharmacol. 1996 Jul;28(1):167-74. doi: 10.1097/00005344-199607000-00024.

DOI:10.1097/00005344-199607000-00024

PMID:8797151

Abstract

We wished to determine whether enhanced bioavailability of bradykinin (BK) and vasodilatory prostaglandins contribute to renovascular and sodium-handling effects of angiotensin-converting enzyme (ACE) inhibition after myocardial infarction (MI). We studied rats after coronary artery ligation treated for 3 weeks with captopril or losartan (2 g/L drinking water for each agent). Hemodynamic and renal function studies were performed in conscious rats before and after sequential infusion BK inhibitor (BKI, 0.02 ng/kg/min) and indomethacin (1 mg/kg). Myocardial infarction increased filtration fraction (FF) 20% (p < .004) but did not change glomerular filtration rate (GFR), urine flow (UF), renal blood flow (RBF), renal vascular resistance (RVR), urine sodium (UNa), or fractional excretion of sodium (FENa). Captopril decreased (p < 0.001) mean arterial pressure (MAP) 25%, UF 61%, RVR 65%, and FENa 75% and increased (p < 0.05) GFR 22%, and RBF 34%. Losartan decreased (p < 0.05) MAP 27%, UF 52%, RVR 21%, and FENa 44%. In captopril-treated MI rats, BKI decreased (p < 0.05) GFR 22% and RBF 25% and increased (p < 0.05) RVR 32%, UNa 43%, and FENa 28%, whereas indomethacin decreased (p < 0.05) GFR 24% and increased (p < 0.05) UNa 86% and FENa 112%. In losartan-treated MI rats, BKI increased (p < 0.05) UNa 42% and FENa 60%, whereas indomethacin increased (p < 0.05) UNa 79% and FENa 85%. Activation of the BK and prostaglandin systems may play an important role in regulating renal function during chronic ACE inhibition, primarily by enhancing the renal vasodilatory effects of angiotensin II (AII) blockade.

摘要

我们希望确定缓激肽（BK）生物利用度的提高和血管舒张性前列腺素是否有助于心肌梗死（MI）后血管紧张素转换酶（ACE）抑制对肾血管和钠处理的影响。我们研究了冠状动脉结扎术后用卡托普利或氯沙坦（每种药物在饮用水中的浓度为2 g/L）治疗3周的大鼠。在清醒大鼠中，在连续输注BK抑制剂（BKI，0.02 ng/kg/min）和吲哚美辛（1 mg/kg）之前和之后进行血流动力学和肾功能研究。心肌梗死使滤过分数（FF）增加20%（p < 0.004），但肾小球滤过率（GFR）、尿流量（UF）、肾血流量（RBF）、肾血管阻力（RVR）、尿钠（UNa）或钠排泄分数（FENa）未发生变化。卡托普利使平均动脉压（MAP）降低25%（p < 0.001）、UF降低61%、RVR降低65%、FENa降低75%，并使GFR增加22%，RBF增加34%（p < 0.05）。氯沙坦使MAP降低27%（p < 0.05）、UF降低52%、RVR降低21%、FENa降低44%。在卡托普利治疗的MI大鼠中，BKI使GFR降低22%，RBF降低25%，并使RVR增加32%，UNa增加43%，FENa增加28%（p < 0.05），而吲哚美辛使GFR降低24%，使UNa增加86%，FENa增加112%（p < 0.05）。在氯沙坦治疗的MI大鼠中，BKI使UNa增加42%，FENa增加60%（p < 0.05），而吲哚美辛使UNa增加79%，FENa增加85%（p < 0.05）。BK和前列腺素系统的激活可能在慢性ACE抑制期间调节肾功能中起重要作用，主要是通过增强血管紧张素II（AII）阻断的肾血管舒张作用。