Enalapril increases mitochondrial nitric oxide synthase in heart and liver.

BOVERIS, A.; D´AMICO, G.; LORES ARNAIZ, S.; COSTA, L.

Antioxidants & Redox Signaling

Mary Ann Liebert, Inc. Publishers

Lugar: New York; Año: 2003 vol. 5 p. 691 - 697

1523-0864

Heart and liver mitochondria isolated from rats treated with enalapri, 3-30 mg/kg/day in the drinking water for 7-120 days, showed a time- and dose-dependent increased nitric oxide (NO) production in the range of 14-250%. Heart and liver mitochondria from control rats produced 0.69 and 0.50 nmol of NO/min/mg of protein, respectively, as determined by dual wavelenght spectrophotometry (577-591 nm) following hemoglobin oxidation to methemoglobin. The response to enalapril treatment, attributed to a gene-mediated up-regulation of mitochondrial nitric oxide synthase (mtNOS) activity, was half-maximal at 5-6 days and was maintained up to 120 days. Enalapril-treated animals showed an increased mtNOS functional activity in heart mitochondria that inhibited state 3 O2 uptake (from 22% in control rats to 43%) and increased state 4 hydrogen peroxide (H2O2) production (from 30% in control rats to 52%). Calculated heart intramitochondrial NO and H2O2 steady-state concentrations were increased 66% and 20% respectively, by enalapril treatment. Signaling pathways dependent on mitochondrial NO and H2O2 may account for the beneficial effects of enalapril in aging mammals.