Véniant M, Clozel J P, Heudes D, Banken L, Ménard J
Pharma Division, F. Hoffmann-La Roche, Basel, Switzerland.
J Cardiovasc Pharmacol. 1993 Apr;21(4):544-51. doi: 10.1097/00005344-199304000-00006.
The goal of the present study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (enalapril) and a long-acting calcium antagonist (Ro 40-5967) on cardiac remodeling secondary to renovascular hypertension. For this purpose, two kidney-one clip (2K-1C) hypertensive rats, 6 weeks after renal artery clipping, were either untreated or treated for 5 weeks with equihypotensive doses of enalapril (3 mg/kg/day) and Ro 40-5967 (30 mg/kg/day). At the end of the treatment period, cardiac weight, maximum coronary blood flow ([MCBF], measured in isolated perfused hearts), and interstitial and perivascular collagen volume fraction (measured by morphometry) were evaluated in all rats. Both drugs similarly decreased arterial blood pressure (ABP) for 24 h. Enalapril was more effective than Ro 40-5967 in inducing regression of cardiac hypertrophy. MCBF was decreased in untreated hypertensive rats and was increased to the same extent by both treatments, although not normalized. Interstitial cardiac collagen content after 11 weeks of hypertension was not increased in untreated hypertensive rats. In contrast, the collagen volume fraction measured in the perivascular area was increased in untreated hypertensive rats and this increase was not significantly suppressed by either enalapril or Ro 40-5967. These results show that cardiac hypertrophy, decrease in MCBF and increase in myocardial collagen content, do not evolve in parallel in 2K-1C hypertensive rats. Two antihypertensive treatments, enalapril and Ro 40-5967, increased MCBF to the same extent but had different effects on cardiac hypertrophy despite having equal antihypertensive efficacy.
本研究的目的是比较血管紧张素转换酶（ACE）抑制剂（依那普利）和长效钙拮抗剂（Ro 40-5967）对肾血管性高血压继发心脏重塑的影响。为此，将肾动脉夹闭6周后的两肾一夹（2K-1C）高血压大鼠分为未治疗组，以及用等降压剂量的依那普利（3 mg/kg/天）和Ro 40-5967（30 mg/kg/天）治疗5周的治疗组。在治疗期结束时，评估所有大鼠的心脏重量、最大冠状动脉血流量（[MCBF]，在离体灌注心脏中测量）以及间质和血管周围胶原体积分数（通过形态计量学测量）。两种药物在24小时内均能同等程度地降低动脉血压（ABP）。依那普利在诱导心脏肥大消退方面比Ro 40-5967更有效。未治疗的高血压大鼠的MCBF降低，两种治疗均使其增加到相同程度，尽管未恢复正常。高血压11周后，未治疗的高血压大鼠的心脏间质胶原含量并未增加。相反，未治疗的高血压大鼠血管周围区域的胶原体积分数增加，且依那普利或Ro 40-5967均未显著抑制这种增加。这些结果表明，在2K-1C高血压大鼠中，心脏肥大、MCBF降低和心肌胶原含量增加并非平行发展。两种抗高血压治疗药物，依那普利和Ro 40-5967，尽管具有相同的抗高血压疗效，但使MCBF增加到相同程度，但对心脏肥大的影响不同。
