Burla Adriana K, Neves Mario Fritsch, Oigman Wille, Mandarim-de-Lacerda Carlos A
Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Centre, State University of Rio de Janeiro, Av 28 de Setembro 87 fds 20551-030 Rio de Janeiro, Rio de Janeiro, Brazil.
Int J Cardiol. 2007 Jan 2;114(1):64-70. doi: 10.1016/j.ijcard.2006.01.007. Epub 2006 May 2.
Several studies have shown beneficial effects of eplerenone in hypertension and left ventricular dysfunction, but its action on cardiac and vascular changes secondary to blood pressure elevation are not clear yet.
Twenty-five male spontaneously hypertensive rats (SHR) were assigned into five groups: young SHR (16 weeks), control SHR (22 weeks), and SHR treated by eplerenone (50 mg/kg/day), enalapril (10 mg/kg/day) or eplerenone+enalapril during 6 weeks. Five Wistar male rats were used as reference group. Cardiac structure and aorta were analyzed by stereology and image analysis.
The raise of blood pressure (202+/-3 mm Hg in control SHR) was significantly attenuated by eplerenone (169+/-2 mm Hg) or enalapril (170+/-2 mm Hg, P<0.001 versus control SHR), and more intensely by combined therapy (160+/-2 mm Hg, P<0.01 versus eplerenone or enalapril). The number of cardiomyocytes in left ventricle was preserved in enalapril group (35,660+/-910 versus 16,220+/-730x10(3) in control SHR, P<0.01) but more significantly in eplerenone, alone or combined, groups (38,380+/-439 and 38,660+/-374x10(3), respectively, P<0.001 versus control). The increased connective tissue volume density (35.8+/-1.2%) noted in the left ventricle of control SHR was significantly attenuated by eplerenone (7.4+/-0.8%), enalapril (8.0+/-0.6%) or eplerenone+enalapril (6.0+/-1.1%, P<0.01 treated versus control SHR). Media-to-lumen ratio of intramyocardial arteries was reduced by enalapril, but more significantly by eplerenone alone or combined with enalapril. The increase of media cross-sectional area of aorta in control SHR was attenuated by eplerenone and/or enalapril.
Eplerenone is effective in attenuating cardiovascular remodeling in SHR, confirming the important role of aldosterone in this process.
多项研究已表明依普利酮在高血压和左心室功能障碍方面具有有益作用,但其对继发于血压升高的心脏和血管变化的作用尚不清楚。
将25只雄性自发性高血压大鼠(SHR)分为五组:年轻SHR(16周)、对照SHR(22周),以及在6周内接受依普利酮(50毫克/千克/天)、依那普利(10毫克/千克/天)或依普利酮+依那普利治疗的SHR。五只Wistar雄性大鼠用作参照组。通过体视学和图像分析对心脏结构和主动脉进行分析。
依普利酮(169±2毫米汞柱)或依那普利(170±2毫米汞柱,与对照SHR相比P<0.001)可显著减弱血压升高(对照SHR中为202±3毫米汞柱),联合治疗减弱作用更强(160±2毫米汞柱,与依普利酮或依那普利相比P<0.01)。依那普利组左心室心肌细胞数量得以保留(35,660±910对对照SHR中的16,220±730×10³,P<0.01),但依普利酮单独或联合治疗组更显著(分别为38,380±439和38,660±374×10³,与对照相比P<0.001)。对照SHR左心室中观察到的结缔组织体积密度增加(35.8±1.2%),依普利酮(7.4±0.8%)、依那普利(8.0±0.6%)或依普利酮+依那普利(6.0±1.1%,治疗组与对照SHR相比P<0.01)可显著减弱。依那普利可降低心肌内动脉的中膜与管腔比值,但依普利酮单独或与依那普利联合使用时作用更显著。对照SHR主动脉中膜横截面积的增加被依普利酮和/或依那普利减弱。
依普利酮可有效减弱SHR的心血管重塑,证实醛固酮在此过程中的重要作用。