Frohlich E D, Horinaka S
Alton Ochsner Medical Foundation, New Orleans, La 70121.
Hypertension. 1991 Oct;18(4 Suppl):II2-7. doi: 10.1161/01.hyp.18.4_suppl.ii2.
The effects of six angiotensin converting enzyme inhibitors (captopril, CGS-16617, cilazapril, enalapril, utibapril, and quinapril) on cardiovascular structure, systemic hemodynamics, left ventricular end-diastolic pressure, left ventricular pumping ability, and aortic distensibility were assessed in male normotensive Wistar-Kyoto and spontaneously hypertensive rats 16-19 weeks of age. Rats (10 in each group) were treated for 3 weeks with drugs or control diluents administered daily by gavage. The agents, in general, had similar hemodynamic effects, although these effects on cardiac mass were variable; some agents reduced left ventricular mass and some produced no change. These effects occurred in hypertrophied as well as nonhypertrophied chambers. Furthermore, changes in left ventricular pumping ability were not necessarily related to the ability of these agents to change left ventricular mass; this dissociation in performance was neither related to change in structure nor to changes in aortic distensibility. Thus, even within a same class of antihypertensive agents (i.e., angiotensin converting enzyme inhibitors), similarly induced hemodynamic alterations were associated with inconsistent changes in left ventricular pumping ability or aortic distensibility regardless of whether the structure was hypertrophied before therapy. These dissociated responses in cardiovascular structure and function may be related to pharmacodynamic or pharmacokinetic differences; alternatively, they also may be related to these differences in action on local myocytic renin-angiotensin systems or in intramyocytic biological responses.
在16 - 19周龄的雄性正常血压Wistar - Kyoto大鼠和自发性高血压大鼠中,评估了六种血管紧张素转换酶抑制剂(卡托普利、CGS - 16617、西拉普利、依那普利、乌替普利和喹那普利)对心血管结构、全身血流动力学、左心室舒张末期压力、左心室泵血能力和主动脉扩张性的影响。大鼠(每组10只)通过灌胃每日给予药物或对照稀释剂,治疗3周。一般来说,这些药物具有相似的血流动力学效应,尽管它们对心脏质量的影响各不相同;一些药物可减轻左心室质量,而一些则无变化。这些效应在肥厚和未肥厚的心室中均有发生。此外,左心室泵血能力的变化不一定与这些药物改变左心室质量的能力相关;这种性能上的分离既与结构变化无关,也与主动脉扩张性变化无关。因此,即使在同一类抗高血压药物(即血管紧张素转换酶抑制剂)中,类似诱导的血流动力学改变也与左心室泵血能力或主动脉扩张性的不一致变化相关,无论治疗前结构是否肥厚。心血管结构和功能中的这些分离反应可能与药效学或药代动力学差异有关;或者,它们也可能与对局部心肌细胞肾素 - 血管紧张素系统的作用差异或心肌细胞内生物学反应差异有关。