Chronic effects of ANG II antagonist in heart failure: improvement of cGMP generation from ANP.
Chronic effects of ANG II antagonist in heart failure: improvement of cGMP generation from ANP.
复制标题
ANG II 拮抗剂对心力衰竭的慢性影响：改善 ANP 生成 cGMP。
DOI：
10.1152/ajpheart.1997.272.5.h2139
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
M. Kinoshita
中科院分区：
文献类型：
--
作者：
Y. Maeda;A. Wada;T. Tsutamoto;D. Fukai;M. Kinoshita
为了评价内源性血管紧张素II（ANG II）对充血性心力衰竭（CHF）发展的影响，我们在快速右心室起搏诱导的CHF犬中长期给予ANG II 1型受体拮抗剂TCV-116后，检测了心肾和激素因素。起搏8天后，开始TCV-116给药[1（组1）或3 mg.kg-1. day-1（组2）]，并持续至第22天。发现TCV-116保护心肾功能的恶化和神经激素因子的激活。尽管TCV-116治疗组之间的肺毛细血管楔压或血浆心钠素（ANP）水平无显著差异，（第1组和第2组分别为354 +/- 85和364 +/- 29 pg/ml）和溶媒组（385 +/-20 pg/ml），血浆鸟苷3 '，5'-环磷酸（cGMP）水平，ANP的第二信使，在TCV-116给药组中高两倍（第1组和第2组分别为49.4 +/- 10.2和50.6 +/- 7.7 pmol/ml）（24 ± 4.0pmol/ml），血浆ANP与cGMP水平高度相关（r = 0.90; P < 0.05）。这些研究结果表明，内源性血管紧张素II在CHF的发展过程中，这可能是由于，部分地，在内源性心钠素活性的降低，提示有用的血管紧张素II受体拮抗剂对CHF的发展血液动力学和肾功能的重要作用。
To evaluate the effects of endogenous angiotensin II (ANG II) on the development of congestive heart failure (CHF), we examined cardiorenal and hormonal factors after chronic administration of the ANG II type 1 receptor antagonist TCV-116 in dogs with CHF induced by rapid right ventricular pacing. After 8 days of pacing, TCV-116 administration [1 (group 1) or 3 mg.kg-1.day-1 (group 2)] was started and continued until the 22nd day. TCV-116 was found to have protected the deterioration of cardiorenal functions and the activation of neurohormonal factors. Although there was no significant difference in the pulmonary capillary wedge pressure or plasma atrial natriuretic peptide (ANP) level between the TCV-116-treated groups (354 +/- 85 and 364 +/- 29 pg/ml for groups 1 and 2, respectively) and the vehicle group (385 +/- 20 pg/ml), the plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels, a second messenger of ANP, were twofold higher in TCV-116-treated groups (49.4 +/- 10.2 and 50.6 +/- 7.7 pmol/ml for groups 1 and 2, respectively) than in the vehicle group (24 +/- 4.0 pmol/ml), with a high correlation between the plasma ANP and cGMP levels (r = 0.90; P < 0.05). These findings indicate that endogenous ANG II has important roles in hemodynamics and renal functions during the development of CHF, which may be due, in part, to a reduction in endogenous ANP activity, suggesting the usefulness of an ANG II-receptor antagonist against the development of CHF.