Zhang Rui-ying, Huang Yong-lin, Sun Yi-hong
Department of Cardiology, First Hospital of Harbin Medical University, Harbin 150001, China.
Zhonghua Yi Xue Za Zhi. 2005 Apr 20;85(15):1053-6.
To evaluate the effects of ACEI, AT1 receptor antagonism, and combination of these two drugs on ventricular remodeling, and the vary of eNOS in rats with myocardial infarction (MI).
Eighty-six rats were randomly divided into four groups at twenty-four hours after MI, and treated for 2 weeks and 6 weeks. (1) MI-placebo (n = 22); (2) MI-Fosinopril (n = 20, 10 mg.kg(-1).d(-1)); (3) MI-Irbesartan (n = 23, 50 mg.kg(-1).d(-1)); (4) MI-Fosinopril + Irbesartan (n = 21, 10 mg.kg(-1).d(-1) + 50 mg.kg(-1).d(-1)); and sham-ligation. Mean blood pressure and left ventricular end diastolic pressure (LVEDP) were evaluated, as well as ventricular weight (VW)/body weight (BW) ratio. The total collagen was quantified by histomorphometry. The expressions of eNOS mRNA and protein within the noninfarction zone were determined by RT-PCR and histomorphometry.
Acute myocardial infarction resulted in a significant increase of LVEDP (P < 0.05), LVDd (P < 0.01), and VW/BW (P < 0.01), and total collagen (at 2 weeks 6.1 +/- 0.7 vs 3.6 +/- 0.5 and at 6 weeks 5.1 +/- 0.8 vs 3.6 +/- 0.4, P < 0.01) in noninfarcted region. Treatment with fosinopril, irbesartan and combination of these two drugs improved them. At the sixth week, irbesartan and combination therapy decreased more significantly total collagen compared with fosinopril (3.4 +/- 0.7 and 3.3 +/- 0.7 vs 4.2 +/- 0.6, P < 0.05). The level of eNOS mRNA expression increased more significantly in combination therapy group than in fosinopril or irbesartan group alone (at 2 weeks 1.55 +/- 0.17, at 6 weeks 1.61 +/- 0.16, P < 0.01). eNOS protein increased.
Fosinopril or irbesartan alone, and combination of these two drugs can improve hemodynamics, limited myocardial hypertrophy, attenuated the development of myocardial interstitial fibrosis in the noninfarcted left ventricule. The use of irbesartan, especially combined with fosinopril was more effective than fosinopril alone in the suppression interstitial fibrosis. Combination therapy was more effective than fosinopril and irbesartan alone in enhancing eNOS mRNA and protein expression.
评估血管紧张素转换酶抑制剂（ACEI）、血管紧张素Ⅱ1型受体拮抗剂（AT1受体拮抗剂）以及二者联合用药对心肌梗死（MI）大鼠心室重构及内皮型一氧化氮合酶（eNOS）变化的影响。
86只大鼠在心肌梗死后24小时随机分为四组，治疗2周和6周。（1）MI-安慰剂组（n = 22）；（2）MI-福辛普利组（n = 20，10 mg·kg⁻¹·d⁻¹）；（3）MI-厄贝沙坦组（n = 23，50 mg·kg⁻¹·d⁻¹）；（4）MI-福辛普利+厄贝沙坦组（n = 21，10 mg·kg⁻¹·d⁻¹ + 50 mg·kg⁻¹·d⁻¹）；以及假结扎组。评估平均血压和左心室舒张末期压力（LVEDP），以及心室重量（VW）/体重（BW）比值。通过组织形态计量学对总胶原进行定量。采用逆转录聚合酶链反应（RT-PCR）和组织形态计量学测定非梗死区eNOS mRNA和蛋白的表达。
急性心肌梗死导致LVEDP（P < 0.05）、左心室舒张末期内径（LVDd，P < 0.01）、VW/BW（P < 0.01）以及非梗死区总胶原显著增加（2周时6.1±0.7 vs 3.6±0.5，6周时5.1±0.8 vs 3.6±0.4，P < 0.01）。福辛普利、厄贝沙坦及二者联合用药治疗可改善上述指标。在第6周时，与福辛普利相比，厄贝沙坦及联合治疗使总胶原减少更显著（3.4±0.7和3.3±0.7 vs 4.2±0.6，P < 0.05）。联合治疗组eNOS mRNA表达水平升高比单独使用福辛普利或厄贝沙坦组更显著（2周时1.55±0.17，6周时1.61±0.16，P < 0.01）。eNOS蛋白增加。
单独使用福辛普利或厄贝沙坦以及二者联合用药均可改善血流动力学，限制心肌肥大，减轻非梗死左心室心肌间质纤维化的发展。使用厄贝沙坦，尤其是与福辛普利联合使用，在抑制间质纤维化方面比单独使用福辛普利更有效。联合治疗在增强eNOS mRNA和蛋白表达方面比单独使用福辛普利和厄贝沙坦更有效。
