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


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 microM 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 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.
Koivisto
A
A
Department of Physiology, University of Uppsala, Sweden. Ari-Pekka.Koivisto@utu.fi
Pittner
J
J
Froelich
M
M
Persson
A E
AE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen