Effect of furosemide-induced hypokalemic metabolic alkalosis on renal transport enzymes.
Hypokalemic metabolic alkalosis is one of the most common complications of chronic furosemide administration. In this study we examined acid-base composition and ATPase enzyme activities in medullary thick ascending limb of Henle's loop (MTAL) and collecting tubule ( CCT and MCT) after seven days of chronic furosemide therapy. All of the studies were conducted in adrenal intact (AI) rats or in adrenalectomized (ADX) glucocorticoid replete rats replaced with a physiological dose of aldosterone (Aldo). Furosemide (F) was administered to each rat by mini-osmotic pump. In the AI+F group, plasma Aldo was high and obvious metabolic alkalosis occurred (HCO3- = 37 +/- 2 mEq/liter vs. 22 +/- 2 mEq/liter in controls, P < 0.005); activities of H-K-ATPase, H-ATPase, and Na-K-ATPase were increased approximately twofold in both CCT and MCT. In the ADX+F group (HCO3- = 28 +/- 2 mEq/liter, P < 0.05 from control), H-ATPase activity was normal in CCT and it was slightly increased in MCT. CCT and MCT H-K-ATPase activities were markedly increased (approximately twofold). Na-K-ATPase activity was the same as control in CCT but it was increased in MCT. In ADX+F+Vanadate (V) group which also had normal Aldo levels, acid-base changes were modest (20 +/- 2 mEq/liter, NS from control); in CCT and MCT H-K-ATPase and Na-K-ATPase activities were markedly reduced, but H-ATPase activity in MCT was increased. In all three experimental groups Na-K-ATPase activity in MTAL was reduced fivefold. Hypokalemia developed in both intact and ADX animals receiving furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)[1]References
- Effect of furosemide-induced hypokalemic metabolic alkalosis on renal transport enzymes. Eiam-Ong, S., Kurtzman, N.A., Sabatini, S. Kidney Int. (1993) [Pubmed]
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