In order to clarify the effects on sodium reabsorption in the loop of Henle of methazolamide (a carbonic anhydrase inhibitor), chlorothiazide and the loop diuretics frusemide and bumetanide, superficial loops were perfused in vivo in anaesthetized rats and the individual diuretics were included in the perfusate. Differentiation between effects in the pars recta and in the thick ascending limb of Henle (TALH) was achieved by comparing responses to the diuretics when using a standard perfusate, designed to mimic native late proximal tubular fluid, and a low-sodium perfusate, designed to block net sodium reabsorption in the pars recta. With the standard perfusate, methazolamide caused decreases in sodium reabsorption (JNa) and water reabsorption (JV); with the low-sodium perfusate, a modest effect on JNa persisted, suggesting that carbonic anhydrase inhibition reduces sodium reabsorption in both the pars recta and the TALH. The effects of chlorothiazide were very similar to those of methazolamide with both the standard and low-sodium perfusates, suggesting that chlorothiazide also inhibits sodium reabsorption in the pars recta and TALH, perhaps through inhibition of carbonic anhydrase. With the standard perfusate, both frusemide and bumetanide produced the expected large decreases in JNa, but JV was also lowered. With the low-sodium perfusate, the inhibitory effects of the loop diuretics, particularly those of frusemide, were substantially reduced, while net potassium secretion was found. These observations indicate that a significant component of the effect of frusemide (and possibly of bumetanide) on overall sodium reabsorption is located in the pars recta, and that loop diuretics induce potassium secretion in the TALH.
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Research Article|
March 22 2000
Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats
R. J. UNWIN;
R. J. UNWIN
*Centre for Nephrology, Royal Free and University College Medical School, Institute of Urology and Nephrology, Middlesex Hospital, London W1N 8AA, U.K.
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S. J. WALTER;
S. J. WALTER
† Division of Biomedical Sciences, Imperial College School of Medicine, Charing Cross Hospital, London W6 8RF, U.K.
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G. GIEBISCH;
G. GIEBISCH
‡Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, U.S.A.
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G. CAPASSO;
G. CAPASSO
§Chair of Nephrology, Second University of Naples, Naples, Italy
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D. G. SHIRLEY
*Centre for Nephrology, Royal Free and University College Medical School, Institute of Urology and Nephrology, Middlesex Hospital, London W1N 8AA, U.K.
Correspondence: Dr D. G. Shirley (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
December 03 1999
Accepted:
January 10 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 98 (4): 481–488.
Article history
Received:
December 03 1999
Accepted:
January 10 2000
Citation
R. J. UNWIN, S. J. WALTER, G. GIEBISCH, G. CAPASSO, D. G. SHIRLEY; Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats. Clin Sci (Lond) 1 April 2000; 98 (4): 481–488. doi: https://doi.org/10.1042/cs0980481
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