Cardiac mitochondrial function and tissue remodelling are improved by a non-antihypertensive dose of enalapril in spontaneously hypertensive rats.
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.
Piotrkowski
Barbara
B
Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina. barbara@ffyb.uba.ar
Koch
Osvaldo R
OR
De Cavanagh
Elena M V
EM
Fraga
César G
CG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control; D004656:Enalapril / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat