血管紧张素II 1型受体拮抗剂以及血管紧张素转换酶抑制剂可减轻主动脉腔静脉瘘大鼠心力衰竭的发展。

Angiotensin II type-1 receptor antagonist as well as angiotensin converying enzyme inhibitor attenuates the development of heart failure in aortocaval fistula rats.

作者信息

Nishikimi T, Tani T, Ohmura T, Yamagishi H, Yanagi S, Yoshiyama M, Toda I, Teragaki M, Akioka K, Takeuchi K

机构信息

First Department of Internal Medicine, Osaka City University Medical School, Japan.

出版信息

Jpn Circ J. 1995 Nov;59(11):754-61. doi: 10.1253/jcj.59.754.

DOI:10.1253/jcj.59.754

PMID:8747765

Abstract

OBJECTIVES

We investigated the effect of chronic administration of an angiotensin II type-1 receptor antagonist in the development of heart failure due to volume overload in rats.

METHODS

Aortocaval fistula (AVF), a model of volume overloaded heart failure, was induced in rats by our newly developed technique using a simple and rapid 18-gauge needle multipuncture. After 3 weeks of oral administration of an angiotensin II receptor antagonist TCV-116, 1 mg/kg per day, we evaluated the hemodynamics, heart weight, and degree of left ventricular dilatation. We also compared the effect of TCV-116 with that of an angiotensin-converting enzyme inhibitor delapril, 1 g/L in drinking water.

RESULTS

AVF heart failure produced by our technique exhibited significant increases in the left ventricular end-diastolic pressure (LVEDP) (12 = 1 vs 4 +/- 1 mmHg, p < 0.05), right atrial pressure (RAP) (5.0 +/- 0.6 vs 1.0 +/- 0.4 mmHg, p < 0.05), right ventricular systolic pressure (RVSP) (58 +/- 6 vs 33 +/- 1 mmHg, p < 0.05), left ventricular weight (LVW) (3.00 +/- 0.13 vs 2.09 +/- 0.04 g/kg BW, p < 0.05), right ventricular weight (RVW) (0.93 +/- 0.05 vs 0.59 +/- 0.01 g/kg BW, p < 0.05), and left ventricular end-diastolic volume index (LVEDVI) (2.55 +/- 0.14 vs 0.80 +/- 0.12 ml/kg BW, p < 0.05) as compared with these values in sham-operated rats. There were no differences in shunt ratio between untreated and TCV-116- and delapril-treated AVF groups. TCV-116 improved these hemodynamics, as did delapril (TCV-116 vs delapril: LVEDP 8 +/- 1 vs 8 +/- 1, RAP: 3.8 +/- 0.6 vs 2.3 +/- 1.4, RASP: 50 +/- 2 vs 46 +/- 3, LVW: 2.53 +/- 0.11 vs 2.52 +/- 0.15, RVW: 0.80 +/- 0.04 vs 0.77 +/- 0.06, LVEDVI: 1.67 +/- 0.15 vs 1.70 +/- 0.17).

CONCLUSION

These results suggest that AVF rats with volume overload produced by a new multipuncture method exhibit both right- and left-side heart failure. Angiotensin II type-1 receptor antagonist as well as angiotensin converting enzyme inhibitor attenuate the development of this type of heart failure in rats.

摘要

目的

我们研究了长期给予1型血管紧张素II受体拮抗剂对大鼠容量超负荷所致心力衰竭发展的影响。

方法

采用我们新开发的技术，用一根简单快速的18号针头多次穿刺，在大鼠身上诱导建立容量超负荷心力衰竭模型——主动脉腔静脉瘘（AVF）。在每天口服1 mg/kg血管紧张素II受体拮抗剂TCV - 116 3周后，我们评估了血流动力学、心脏重量和左心室扩张程度。我们还将TCV - 116的效果与饮用水中含1 g/L血管紧张素转换酶抑制剂地拉普利的效果进行了比较。

结果

与假手术大鼠相比，我们的技术所产生的AVF心力衰竭大鼠的左心室舒张末期压力（LVEDP）（12 = 1 vs 4±1 mmHg，p < 0.05）、右心房压力（RAP）（5.0±0.6 vs 1.0±0.4 mmHg，p < 0.05）、右心室收缩压（RVSP）（58±6 vs 33±1 mmHg，p < 0.05）、左心室重量（LVW）（3.00±0.13 vs 2.09±0.04 g/kg体重，p < 0.05）、右心室重量（RVW）（0.93±0.05 vs 0.59±0.01 g/kg体重，p < 0.05）以及左心室舒张末期容积指数（LVEDVI）（2.55±0.14 vs 0.80±0.12 ml/kg体重，p < 0.05）均显著增加。未治疗组与TCV - 116治疗组和地拉普利治疗组的AVF大鼠之间的分流率没有差异。TCV - 116改善了这些血流动力学指标，地拉普利也有同样效果（TCV - 116与地拉普利比较：LVEDP 8±1 vs 8±1，RAP：3.8±0.6 vs 2.3±1.4，RASP：50±2 vs 46±3，LVW：2.53±0.11 vs 2.52±0.15，RVW：0.80±0.04 vs 0.77±0.06，LVEDVI：1.67±0.15 vs 1.70±0.17）。