Oxygen-dependent inhibition of respiration in isolated renal tubules by nitric oxide

Autor: Matteus Froelich, Ari Koivisto, Janos Pittner, A. Erik G. Persson
Rok vydání: 1999
Předmět:
Zdroj: Kidney International. 55(6):2368-2375
ISSN: 0085-2538
DOI: 10.1046/j.1523-1755.1999.00474.x
Popis: Oxygen-dependent inhibition of respiration in isolated renal tubules by nitric oxide. Background The partial pressure (tension) of oxygen (P O 2 ) in the kidney medulla has been established to be lower than that of the cortex. The kidney medulla has been shown to be particularly sensitive to hypoxia. However, the measured P O 2 in the kidney medulla is sufficient to support maximal respiration. It has been recently shown that endogenously produced nitric oxide (NO) may inhibit oxygen consumption in the kidney. We studied whether NO plays a role in hypersensitivity of the kidney medulla to hypoxia. Methods We studied the effect of added NO on isolated cortical and outer medullary renal tubules in simultaneous oxygen consumption and NO measurements at different oxygen concentrations. Results We found that NO could potently and reversibly inhibit respiration at nanomolar concentrations. The inhibitory effect of NO was markedly increased at low physiological oxygen concentrations. The effect of NO was cGMP independent because the selective guanylyl cyclase inhibitor 1H- 1,2,4 oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) at a 10 μm concentration had no effect on basal or NO-inhibited respiration. The value for half-maximal NO-mediated inhibition of respiration was virtually identical to that found in isolated mitochondria, and therefore, NO was most likely directly acting on mitochondria. Interestingly, we found no differences in sensitivity to NO-mediated inhibition between outer medullary and cortical tubules. Conclusions We suggest that because of its low P O 2 , the renal outer medulla is more sensitive to hypoxia, not because of the low P O 2 as such, but probably because of the competition between NO and oxygen to control respiration.
Databáze: OpenAIRE