Yonezawa T, Umemoto S, Fujii A, Katayama K, Matsuzaki M
2nd Department of Internal Medicine, Yamaguchi University School of Medicine, Japan.
J Cardiovasc Pharmacol. 1996 Jan;27(1):119-24. doi: 10.1097/00005344-199601000-00019.
We compared the cardiac effects of the selective angiotensin II type 1 (AT1)-receptor blockade, FK-739, with an angiotensin-converting-enzyme (ACE) inhibitor, enalapril, on left ventricular (LV) distensibility and collagen metabolism in spontaneously hypertensive rats (SHRs). We treated 14-week-old SHRs with FK-739 (30 mg/kg/day) or enalapril (10 mg/kg/day) for 6 weeks. Both FK-739 and enalapril induced a significant decrease in blood pressure (p < 0.001) and regression of LV hypertrophy (p < 0.001) compared with vehicle, with no differences between the treated groups. Furthermore, FK-739 caused a greater decrease in LV collagen content than did enalapril (FK-739-treated group, 3.06 +/- 0.11 mg/g; enalapril-treated group, 3.47 +/- 0.05 mg/g; p = 0.015) with no change in collagen phenotypes. Hearts taken from rats treated with FK-739 also showed greater LV distensibility than those taken from enalapril-treated rats (FK-739-treated group vs. enalapril-treated group at > or = 15 mm Hg, p < 0.001). These results suggest that, compared with ACE inhibition, AT1-receptor blockade may have additional effects on LV distensibility and collagen metabolism in the regression of LV hypertrophy induced by pressure overload.
我们比较了选择性血管紧张素II 1型（AT1）受体阻滞剂FK-739与血管紧张素转换酶（ACE）抑制剂依那普利对自发性高血压大鼠（SHR）左心室（LV）舒张性和胶原代谢的心脏效应。我们用FK-739（30毫克/千克/天）或依那普利（10毫克/千克/天）治疗14周龄的SHR，为期6周。与赋形剂相比，FK-739和依那普利均显著降低血压（p < 0.001）并使左心室肥厚消退（p < 0.001），治疗组之间无差异。此外，FK-739使左心室胶原含量的降低幅度大于依那普利（FK-739治疗组，3.06 +/- 0.11毫克/克；依那普利治疗组，3.47 +/- 0.05毫克/克；p = 0.015），且胶原表型无变化。取自FK-739治疗大鼠的心脏也比取自依那普利治疗大鼠的心脏表现出更大的左心室舒张性（FK-739治疗组与依那普利治疗组在≥15毫米汞柱时，p < 0.001）。这些结果表明，与ACE抑制相比，AT1受体阻断在压力超负荷诱导的左心室肥厚消退过程中可能对左心室舒张性和胶原代谢有额外作用。
