Nunez E, Hosoya K, Susic D, Frohlich E D
Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, La 70121, USA.
Hypertension. 1997 Jan;29(1 Pt 2):519-24. doi: 10.1161/01.hyp.29.1.519.
Among the multiple mechanisms postulated for the increased risk of hypertensive left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a strong possibility. This study was designed to compare the effects of treatment with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two renin-angiotensin system (RAS) inhibitor would be as or more effective in reducing mean arterial pressure (MAP), left ventricular (LV) mass, and improving coronary hemodynamics than either regimen alone. Thus, 23 week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap water (C), enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1), or their combination (15 mg.kg-1.d-1). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls. After 12 weeks, systemic and coronary hemodynamics were determined (15 microns radiolabeled microspheres) at baseline, during maximal treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and losartan equally reduced MAP and LV mass in association with a decreased total peripheral resistance. The RAS combination reduced MAP and LV mass more than either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit of LV mass did not differ among the groups. Although enalapril did not improve coronary flow reserve (CFR), it diminished minimal coronary vascular resistance (MCVR); losartan improved both. However, the combination was more effective than either agent alone, reaching values close to normotensive WKY controls. In conclusion, these data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapril improved systemic and coronary hemodynamics more than enalapril alone.
在为高血压性左心室肥厚（LVH）风险增加所假定的多种机制中，冠状动脉血流动力学改变仍是一个很大的可能性。本研究旨在比较用血管紧张素转换酶（ACE）抑制剂（依那普利）和血管紧张素AT1受体拮抗剂（氯沙坦）治疗对全身和冠状动脉血流动力学的影响，并确定这两种肾素 - 血管紧张素系统（RAS）抑制剂联合使用在降低平均动脉压（MAP）、左心室（LV）质量以及改善冠状动脉血流动力学方面是否与单独使用任一疗法一样有效或更有效。因此，对23周龄的自发性高血压大鼠（SHR）用自来水（C）、依那普利（30 mg·kg-1·d-1）、氯沙坦（30 mg·kg-1·d-1）或它们的组合（15 mg·kg-1·d-1）进行治疗（12周）。年龄匹配的Wistar - Kyoto（WKY）大鼠作为正常血压对照。12周后，在基线、最大跑步机运动期间以及最大扩张（双嘧达莫）期间测定全身和冠状动脉血流动力学（15微米放射性标记微球）。依那普利和氯沙坦在降低总外周阻力的同时，同等程度地降低了MAP和LV质量。RAS组合降低MAP和LV质量的效果比单独使用任一药物更显著。静息心指数和每单位LV质量的冠状动脉血流量（CBF）在各组之间没有差异。虽然依那普利没有改善冠状动脉血流储备（CFR），但它降低了最小冠状动脉血管阻力（MCVR）；氯沙坦则两者都有改善。然而，联合使用比单独使用任一药物更有效，达到接近正常血压WKY对照的值。总之，这些数据表明未治疗的SHR中最大CBF、CFR和MCVR显著受损，但单独使用氯沙坦以及与依那普利联合使用比单独使用依那普利更能改善全身和冠状动脉血流动力学。
