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

1999; Elsevier BV; Volume: 55; Issue: 6 Linguagem: Inglês

10.1046/j.1523-1755.1999.00474.x

1523-1755

Ari Koivisto, János Pittner, Matteus Froelich, A. Erik G. Persson,

Hemoglobin structure and function

Oxygen-dependent inhibition of respiration in isolated renal tubules by nitric oxide.BackgroundThe partial pressure (tension) of oxygen (PO2) 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 PO2 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.MethodsWe 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.ResultsWe 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.Deetjen P. Kramer K. Die abhängigkeit der O2-verbrauches der niere von der Na-rückresorption.Pflügers Arch. 1961; 272: 636-650Crossref Scopus (86) Google Scholar, 2.Kiil F. Aukland K. Refsum H.E. Renal sodium transport and oxygen consumption.Am J Physiol. 1961; 201: 511-516PubMed Google Scholar, 4.Ullrich K.J. Pehling G. Aktiver natriumtransport und sauerstoffverbrauch in der äusseren markzone der niere.Pflügers Arch. 1958; 267: 207-217Crossref PubMed Scopus (14) Google Scholaroxadiazolo[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.ConclusionsWe suggest that because of its low PO2, the renal outer medulla is more sensitive to hypoxia, not because of the low PO2 as such, but probably because of the competition between NO and oxygen to control respiration. Oxygen-dependent inhibition of respiration in isolated renal tubules by nitric oxide. The partial pressure (tension) of oxygen (PO2) 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 PO2 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. 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. 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.Deetjen P. Kramer K. Die abhängigkeit der O2-verbrauches der niere von der Na-rückresorption.Pflügers Arch. 1961; 272: 636-650Crossref Scopus (86) Google Scholar, 2.Kiil F. Aukland K. Refsum H.E. Renal sodium transport and oxygen consumption.Am J Physiol. 1961; 201: 511-516PubMed Google Scholar, 4.Ullrich K.J. Pehling G. Aktiver natriumtransport und sauerstoffverbrauch in der äusseren markzone der niere.Pflügers Arch. 1958; 267: 207-217Crossref PubMed Scopus (14) Google Scholaroxadiazolo[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. We suggest that because of its low PO2, the renal outer medulla is more sensitive to hypoxia, not because of the low PO2 as such, but probably because of the competition between NO and oxygen to control respiration.