Effects of furosemide on medullary oxygenation in younger and older subjects

Abstract

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. 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.