Effects of furosemide on medullary oxygenation in younger and older subjects

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

Multiple pumps for sodium reabsorption by the perfused kidney

Multiple pumps for sodium reabsorption by the perfused kidney. Several distinct transport mechanisms responsible for sodium reabsorption by the rat kidney can be identified by studying the function of isolated perfused kidneys. Approximately one-half of the fractional sodium reabsorption by the isolated perfused rat kidney appears to depend on Na-K-adenosine triphosphatase (AT-Pase) and is inhibited by ouabain. About 15 to 20% is associated with the reabsorption of bicarbonate and is blocked by acetazolamide. This fraction of transported sodium is unaffected by ouabain and therefore does not involve Na-K-ATPase. Neither furosemide nor ethacrynic acid produce further inhibition of sodium reabsorption in a kidney already exposed to ouabain and acetazolamide. Most of the residual transport of sodium is inhibited by cooling the perfused kidney, suggesting that it is powered by metabolic rather than physical sources of energy.Multiplicité des pompes qui assurent la réabsorption du sodium par le rein perfusé. Plusieurs mécanismes de transport distincts responsables de la réabsorption de sodium par le rein de rat peuvent être identifiés par l'étude du fonctionnement de reins isolés perfusés. La moitié, approximativement, de la réabsorption fractionnelle du sodium par les reins isolés perfusés semble dépendre de la Na-K-ATPase et est inhibée par l'ouabaïne. Environ 15 à 20% sont associes à la réabsorption du bicarbonate et bloqués par l'acetazolamide. Cette fraction du sodium transporté n'est pas affectée par l'ouabaïne et donc n'implique pas la Na-K-ATPase. Ni le furosémide ni l'acide éthacrynique ne produisent d'inhibition supplémentaire de la réabsorption de sodium par un rein déjà exposé à l'ouabaïne et à l'acetazolamide. La plus grande partie du transport résiduel du sodium est inhibée par le refroidissement du rein perfusé, ce qui suggère une source d'énergie métabolique plutôt que physique

Adaptation to potassium

In vertebrates, the development of complex and efficient mechanisms for avoiding potassium intoxication might be predicted from a simple consideration of their chemical anatomy. The proper function of excitable membranes depends on a low concentration of potassium outside of the cell. On the other hand, potassium is the major ionic constituent of intracellular fluid; it therefore accompanies calories in almost every form of food. Animals that alternate starvation with periods of gorging themselves must therefore be able to adapt to sudden large exogenous loads of potassium in order to avoid potassium intoxication