Hayashida W, Donckier J, Van Mechelen H, Charlier A A, Pouleur H
Department of Physiology and Pharmacology, School of Medicine, University of Louvain, Brussels, Belgium.
Cardiovasc Res. 1997 Jan;33(1):54-62. doi: 10.1016/s0008-6363(96)00194-0.
Angiotensin II has been suggested to be involved in the pathogenesis of diastolic dysfunction in left ventricular hypertrophy (LVH). The purpose of this study was to asses the effects of enalaprilat and L-158,809, an angiotensin II type-1 receptor antagonist, on LV diastolic function in 16 normal control dogs and 20 LVH dogs with perinephritic hypertension.
LV hemodynamics was studied before and after intravenous injection of enalaprilat (0.25 mg/kg) or L-158,809 (0.3 mg/kg). The hemodynamic data were analyzed in relation to the changes in myocardial blood flow (measured by radioactive microspheres) and in the circulating angiotensin II and norepinephrine levels.
At baseline, significant increases were observed for LV/body weight ratio as well as LV systolic and end-diastolic pressure in the LVH dogs (all P < 0.01 vs. the control group). In addition, LV relaxation time constant was prolonged and the chamber and myocardial stiffness constants were increased (P < 0.01) in the LVH dogs, suggesting an impairment of LV diastolic function. Administration of enalaprilat or L-158,809 improved LV stiffness constants in the LVH dogs (P < 0.05). The diastolic LV pressure-diameter relation shifted downwards in the LVH dogs whereas diastolic distensibility was not altered in the control dogs. Although the circulating angiotensin II levels were significantly decreased by enalaprilat in the LVH dogs, they did not correlate with the changes in the stiffness constants. Furthermore, the alterations of LV diastolic properties in the LVH group could not be attributed to myocardial perfusion, which was rather decreased by administration of enalaprilat and L-158,809. These results suggest that angiotensin II, particularly at the local level, is involved in the pathogenesis of diastolic dysfunction in pressure-overload LVH. The data also support the concept that ACE inhibitors and angiotensin II receptor blockers are potentially beneficial in the treatment of the hypertrophied heart.
有研究表明血管紧张素II参与左心室肥厚（LVH）时舒张功能障碍的发病机制。本研究旨在评估依那普利拉和血管紧张素II 1型受体拮抗剂L-158,809对16只正常对照犬和20只患有肾周性高血压的LVH犬左心室舒张功能的影响。
在静脉注射依那普利拉（0.25mg/kg）或L-158,809（0.3mg/kg）前后研究左心室血流动力学。分析血流动力学数据与心肌血流量（通过放射性微球测量）以及循环血管紧张素II和去甲肾上腺素水平变化的关系。
在基线时，LVH犬的左心室/体重比以及左心室收缩压和舒张末期压力显著升高（与对照组相比，均P<0.01）。此外，LVH犬的左心室舒张时间常数延长，心室和心肌硬度常数增加（P<0.01），提示左心室舒张功能受损。给予依那普利拉或L-158,809可改善LVH犬的左心室硬度常数（P<0.05）。LVH犬的舒张期左心室压力-直径关系向下移动，而对照犬的舒张期扩张性未改变。尽管依那普利拉使LVH犬的循环血管紧张素II水平显著降低，但它们与硬度常数的变化无关。此外，LVH组左心室舒张特性的改变不能归因于心肌灌注，依那普利拉和L-158,809给药反而使心肌灌注减少。这些结果表明血管紧张素II，特别是在局部水平，参与压力超负荷LVH时舒张功能障碍的发病机制。数据还支持ACE抑制剂和血管紧张素II受体阻滞剂在治疗肥厚性心脏方面可能有益的观点。
