Piotrkowski Barbara, Koch Osvaldo R, De Cavanagh Elena M V, Fraga César G
Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina.
Free Radic Res. 2009 Apr;43(4):390-9. doi: 10.1080/10715760902801517. Epub 2009 Mar 18.
Renal and cardiac benefits of renin-angiotensin system inhibition exceed blood pressure (BP) reduction and seem to involve mitochondrial function. It has been shown that RAS inhibition prevented mitochondrial dysfunction in spontaneously hypertensive rats (SHR) kidneys. Here, it is investigated whether a non-antihypertensive enalapril dose protects cardiac tissue and mitochondria function. Three-month-old SHR received water containing enalapril (10 mg/kg/day, SHR+Enal) or no additions (SHR-C) for 5 months. Wistar-Kyoto rats (WKY) were normotensive controls. At month 5, BP was similar in SHR+Enal and SHR-C. In SHR+Enal and WKY, heart weight and myocardial fibrosis were lower than in SHR-C. Matrix metalloprotease-2 activity was lower in SHR+Enal with respect to SHR-C and WKY. In SHR+Enal and WKY, NADH/cytochrome c oxidoreductase activity, eNOS protein and activity and mtNOS activity were higher and Mn-SOD activity was lower than in SHR-C. In summary, enalapril at a non-antihypertensive dose prevented cardiac hypertrophy and modifies parameters of cardiac mitochondrial dysfunction in SHR.
肾素-血管紧张素系统抑制对肾脏和心脏的益处超过血压降低,且似乎与线粒体功能有关。研究表明,肾素-血管紧张素系统抑制可预防自发性高血压大鼠(SHR)肾脏的线粒体功能障碍。在此,研究非降压剂量的依那普利是否能保护心脏组织和线粒体功能。3个月大的SHR接受含依那普利的水(10毫克/千克/天,SHR+依那普利组)或不添加任何物质(SHR-C组),持续5个月。Wistar-Kyoto大鼠(WKY)作为血压正常的对照。在第5个月时,SHR+依那普利组和SHR-C组的血压相似。在SHR+依那普利组和WKY组中,心脏重量和心肌纤维化程度均低于SHR-C组。与SHR-C组和WKY组相比,SHR+依那普利组中基质金属蛋白酶-2的活性较低。在SHR+依那普利组和WKY组中,NADH/细胞色素c氧化还原酶活性、内皮型一氧化氮合酶(eNOS)蛋白及活性以及线粒体一氧化氮合酶(mtNOS)活性较高,而锰超氧化物歧化酶(Mn-SOD)活性低于SHR-C组。总之,非降压剂量的依那普利可预防SHR的心脏肥大并改善心脏线粒体功能障碍的参数。