The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (–SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.1 ± 129.3 to 2,928.6 ± 502.0 nM and from 3.8 ± 0.7 to 9.0 ± 1.6 nA before and during ischemia, respectively) that dropped to preischemic levels during reperfusion. OMBF and –SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure was observed (GFR 923.0 ± 66.0 and 253.6 ± 55.3 μl·min−1·g kidney wt−1 in sham-operated and ischemic kidneys, respectively; P < 0.05). The induction of HO-1 (CoCl2 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7 ± 41.0 nM), although endothelial and neuronal NOS expression were slightly increased. CoCl2 administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1,315.6 ± 445.6 nM and 6.3 ± 0.5 nA, respectively; P < 0.05), preserving postischemic OMBF and GFR (686.4 ± 45.2 μl·min−1·g kidney wt−1). These beneficial effects of CoCl2 on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by stannous mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.
Heme Oxygenase-1-Mediated Protection: Potential Role of Nonheme Iron–Nitric Oxide Complexes
