Effect of nitric oxide on ammoniagenesis in rats.

AIM

This in vitro study using rat cortical slices, isolated proximal tubules and mitochondria was conducted to investigate the effect of exogenous and endogenous nitric oxide on ammoniagenesis.

METHODS AND RESULTS

The cortical slices were incubated with phosphate-buffered saline containing 1 mML-glutamine at 37 degrees C andglutamine-stimulated ammoniagenesis which was further elevated with 10(-7)M ANGII showed a time-dependent decrease during 2 h. 10(-4)M L-NAME or 10(-5)ML-canavanin caused a similar ammonia elevation to that of ANGII, whereas the addition of 10(-5)M SNAP attenuated the ammonia-increasing effects of ANGII and L-NAME. Basal or exogenous NO without significantly affecting glutamine uptake of the slices seemed to convert the glutamine deamidation pathway to transamination, since L-NAME increased the ammonia to glutamine ratio from 0.87 +/- 0.08 mol/mol to 1.03 +/- 0.04 (p < 0.01). L-NAME increased both ammoniagenesis and mitochondrial oxygen consumption but SNAP depressed them. Endogenous NO reduced ammoniagenesis without changing the mitochondrial permeability transition pore (PTP), whereas exogenous NO-induced attenuation in ammoniagenesis was associated with elevated PTP in a CsA-sensitive manner.

CONCLUSION

These results demonstrated that in rat kidney, basal NO depresses mitochondrial oxygen consumption and attenuates ammoniagenesis without affecting PTP; however, exogenous NO inhibits ammonia production by disturbing PTP in isolated mitochondria.