IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
artículos
Título:
Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney
Autor/es:
B. PIOTRKOWSKI; C. G. FRAGA; E. M. V. DE CAVANAGH
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY, INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Referencias:
Año: 2007 p. 1497 - 1501
ISSN:
0363-6119
Resumen:
Mitochondrial function
and nitric oxide metabolism are modified by enalapril treatment in rat kidney.
Am J Physiol Regul Integr Comp Physiol 292: R1494R1501, 2007. First
published December 21, 2006; doi:10.1152/ajpregu.00540.2006.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_kg_1 _day_1; Enal), or a NO synthase (NOS) inhibitor,
N_-nitro-L-arginine methyl ester (L-NAME) (1 mg_kg_1 _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
H2O2 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.