Determinants of intrarenal oxygenation. I. Effects of diuretics.
To study renal cortical and medullary oxygen tensions, we used sensitive Clark-type O2 microelectrodes, inserted by micromanipulators into the cortex and medulla of kidneys of anesthetized rats. As previously reported, under basal conditions, medullary PO2 was significantly lower than cortical PO2. Furosemide, which inhibits reabsorptive transport in the medullary thick ascending limb, increased medullary PO2 from 16 +/- 4 to 35 +/- 4 mmHg (P < 0.0005) without altering cortical PO2. This effect, reproduced by ethacrynic acid and bumetanide, was selective for loop diuretics and was directly due to decreased tubular O2 consumption, since medullary blood flow was remarkably reduced by furosemide (-28 +/- 6% from baseline, P < 0.0001, as measured by a laser-Doppler probe). By contrast, acetazolamide, which decreases proximal tubule metabolism, selectively increased cortical PO2. These data are, in general, consistent with tubular metabolism as a major determinant of intrarenal oxygenation and suggest, in particular, that medullary reabsorptive work is at least in part responsible for renal medullary hypoxia.
Brezis
M
M
Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Agmon
Y
Y
Epstein
F H
FH
D000042:Absorption; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000098:blood supply / Q000378:metabolism; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D008839:Microelectrodes; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D004232:Diuretics; D002034:Bumetanide; D008353:Mannitol; D005665:Furosemide; D004976:Ethacrynic Acid; D000086:Acetazolamide