Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats.
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 (J(Na)) and water reabsorption (J(V)); with the low-sodium perfusate, a modest effect on J(Na) 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 J(Na), but J(V) 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.
Unwin
R J
RJ
Centre for Nephrology, Royal Free and University College Medical School, Institute of Urology and Nephrology, Middlesex Hospital, London W1N 8AA, U.K.
Walter
S J
SJ
Giebisch
G
G
Capasso
G
G
Shirley
D G
DG
D000042:Absorption / Q000187:drug effects; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002740:Chlorothiazide / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology; D008138:Loop of Henle / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008704:Methazolamide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000493:pharmacokinetics
D002257:Carbonic Anhydrase Inhibitors; D004232:Diuretics; D002034:Bumetanide; D002740:Chlorothiazide; D005665:Furosemide; D012964:Sodium; D008704:Methazolamide