Effects of furosemide on medullary oxygenation in younger and older subjects.

UNLABELLED Renal medullary hypoxia is characteristic of mammalian kidneys and can be assessed noninvasively in animals and humans by blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). Water diuresis has been shown to improve medullary oxygenation in young human subjects but not in elderly subjects, a difference attributed to a decline in renal prostaglandin production with age. Loop diuretics such as furosemide also increase medullary oxygenation in experimental animals, by inhibiting active transport and oxygen consumption in the medullary thick ascending limb. We examined, using BOLD MRI, this response to furosemide in eight younger (23 to 34 years) and eight elderly (64 to 81 years) healthy women. We also attempted to assess the role of prostaglandins in age-related differences, using ibuprofen to inhibit prostaglandin E2 synthesis. Renal medullary oxygenation, initially low, increased during furosemide diuresis in younger subjects. In the older population, however, furosemide usually elicited little or no change in oxygenation of the renal medulla, despite profuse diuresis. Ibuprofen did not inhibit the action of furosemide to improve medullary pO2 in younger subjects. CONCLUSIONS The action of loop diuretics to improve medullary oxygenation, apparent in younger subjects, is blunted by normal aging. Inhibition of prostaglandin synthesis did not counteract the effect of furosemide in younger subjects, suggesting that a decline in prostaglandin E2 production with age is not the central cause of this age-related defect.

[1]  C. Hill,et al.  Acute renal failure in the elderly. , 1973, Lancet.

[2]  J. Porush,et al.  Effects of Diuretics on Inner Medullary Hemodynamics in the Dog , 1982, Circulation research.

[3]  M. Brezis,et al.  Transport activity modifies thick ascending limb damage in the isolated perfused kidney. , 1984, Kidney international.

[4]  M. Brezis,et al.  The pathophysiological implications of medullary hypoxia. , 1989, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[5]  T. Wilson,et al.  Effects of aging on responses to furosemide. , 1989, Prostaglandins.

[6]  M. Brezis,et al.  Relation of adenosine to medullary injury in the perfused rat kidney. , 1990, Mineral and electrolyte metabolism.

[7]  S. Lankford,et al.  Changes in cytochrome oxidation in outer and inner stripes of outer medulla. , 1991, The American journal of physiology.

[8]  M. Brezis,et al.  Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys. , 1991, The Journal of clinical investigation.

[9]  M. Brezis,et al.  Potential deleterious effect of furosemide in radiocontrast nephropathy. , 1992, Nephron.

[10]  M. Brezis,et al.  Determinants of intrarenal oxygenation. I. Effects of diuretics. , 1994, The American journal of physiology.

[11]  J. D'Elia,et al.  Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. , 1994, The New England journal of medicine.

[12]  F. Epstein,et al.  Urinary prostaglandin E2 and dopamine responses to water loading in young and elderly humans , 1995 .

[13]  R R Edelman,et al.  Noninvasive evaluation of intrarenal oxygenation with BOLD MRI. , 1996, Circulation.

[14]  R R Edelman,et al.  Breath‐hold R2* mapping with a multiple gradient‐recalled echo sequence: Application to the evaluation of intrarenal oxygenation , 1997, Journal of magnetic resonance imaging : JMRI.

[15]  F. Epstein,et al.  Changes in renal medullary pO2 during water diuresis as evaluated by blood oxygenation level-dependent magnetic resonance imaging: effects of aging and cyclooxygenase inhibition. , 1999, Kidney international.