Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney.
The renal and cardiac benefits of renin-angiotensin system (RAS) inhibition in hypertension exceed those attributable to blood pressure reduction, and seem to involve mitochondrial function changes. To investigate whether mitochondrial changes associated with RAS inhibition are related to changes in nitric oxide (NO) metabolism, four groups of male Wistar rats were treated during 2 wk with a RAS inhibitor, enalapril (10 mg x kg(-1) x day(-1); Enal), or a NO synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME) (1 mg x kg(-1) x day(-1)), or both (Enal+L-NAME), or were untreated (control). Blood pressure and body weight were lower in Enal than in control. Electron transfer through complexes I to III and cytochrome oxidase activity were significantly lower, and uncoupling protein-2 content was significantly higher in kidney mitochondria isolated from Enal than in those from control. All of these changes were prevented by L-NAME cotreatment and were accompanied by a higher production/bioavailability of kidney NO. L-NAME abolished mitochondrial NOS activity but failed to inhibit extra-mitochondrial kidney NOS, underscoring the relevance of mitochondrial NO in those effects of enalapril that were suppressed by L-NAME cotreatment. In Enal, kidney mitochondria H(2)O(2) production rate and MnSOD activity were significantly lower than in control, and these effects were not prevented by L-NAME cotreatment. These findings may clarify the role of NO in the interactions between RAS and mitochondrial metabolism and can help to unravel the mechanisms involved in renal protection by RAS inhibitors.
Piotrkowski
Barbara
B
Physical Chemistry-PRALIB, Univ. of Buenos Aires, Junín 956, 1113-Buenos Aires, Argentina.
Fraga
Cesar G
CG
de Cavanagh
Elena M V
EM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000493:pharmacokinetics; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000071246:Uncoupling Protein 2
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D009569:Nitric Oxide; D004656:Enalapril; D006861:Hydrogen Peroxide; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D019331:NG-Nitroarginine Methyl Ester