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Effects of Diuretics on Renal Function

Jules B. Puschett, Joseph Winaver

10.1002/cphy.cp080250

Source: Supplement 25: Handbook of Physiology, Renal Physiology

Originally published: 1992

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Diuretic Effects on Renal Hemodynamics
1.1 Drugs That Primarily Alter Glomerular Function
1.2 Drugs That Primarily Alter Tubular Function
1.3 Diuretic Effects on Intrarenal Blood Flow Distribution
1.4 Diuretic Interactions with the Renin–Angiotensin‐Aldosterone system
1.5 Diuretic Interactions with Prostaglandin Synthesis and with the Inhibition of Prostaglandin Synthetase
2 Nephron Sites of Action and Effects of Diuretics on Solute Excretion
2.1 Review and Comparison of Methodologies
2.2 Utility of the Clearance Technique for the Study of Diuretic Site and Mechanism of Action in Man
2.3 Diuretic Effects on the Excretion of Specific Solutes
3 Cellular and Molecular Actions of Diuretics
3.1 Carbonic Anhydrase Inhibitors
3.2 Loop Diuretics
3.3 Thiazides
3.4 Mineralcorticoid Antagonists
3.5 Amiloride
Figure 1. Figure 1.

Diagram of nephron depicting major sites of electrolyte and water transport. Closed and open arrows represent active and passive transport processes, respectively.

Reproduced from Puschett 465 with permission
Figure 2. Figure 2.

Chemical structures of diuretic drugs, grouped according to chemical class.
Figure 3. Figure 3.

Effects of four diuretics on generation of solute‐free water (CH2O). Each diagram presents data obtained in single representative study performed in normal human subject undergoing maximal steady‐state water diuresis. In each case, drug was given at arrow. COsm, solute clearance; V, urine flow rate; CNa/Cin × 100, percentage of filtered sodium excreted. U/Posm, urinary and plasma osmolality, respectively. A: Acetazolamide. B: Ethacrynic acid. C: Metolazone. D: Chlorothiazide.

From Puschett 462. From Goldberg 242
Figure 4. Figure 4.

Effects of two diuretic agents on reabsorption of solute‐free water (TCH2O) in three normal human volunteers (M. D., W. M. B., and A. G., respectively) undergoing hypertonic saline diuresis during hydropenic conditions. Drug given during progressive increase in distal delivery of salt and water as indicated by increasing values for solute clearance (COsm). A: Bumetanide, 1 mg intravenously administered at time zero. B: Metolazone, (1 mg intravenously) given at arrows to three subjects (▪, •, ▴, respectively). Same subjects (□, ○, Δ, respectively) were then studied at another time during hypertonic saline infusion, without administration of the diuretic, for comparison purposes.

From Jayakumar and Puschett 311. From Steinmuller and Puschett 549
Figure 5. Figure 5.

Effect of chlorothiazide (CTZ) on proton secretion by turtle bladder. Data indicate that, at each pH level, rates of H+ ion secretion were higher following addition of chlorothiazide (1.0 mg/ml) to mucosal surface.

From Lief et al. 363
Figure 6. Figure 6.

Effects of bumetanide (1 mg intravenously) on urinary pH and absolute excretion rates of titratable acid (UtaV), ammonium ion (+V), and bicarbonate (−V) in representative study in man. Dotted line, time zero; triangles, Uph values.

From Jayakumar and Puschett 311
Figure 7. Figure 7.

Change in percentage of filtered potassium excreted (ΔCk/Cln × 100) as function of increment in percentage of filtered sodium excreted (ΔCNa/Cln × 100) following administration of five diuretic agents to normal human volunteers. Dashed line, zero change from control; ECA, ethacrynic acid.

From Puschett and Rastegar 469
Figure 8. Figure 8.

Main transport systems in various nephron segments. Targets for diuretic actions are indicated by the following symbols: ⊗ Na+‐K+ pump; ○ symport or antiport; conductive pathways. A. proximal tubule; B. thick ascending limb of the loop of Henle; C. distal convoluted tubule; D. collecting duct. See text for further details.

From 394 with permission
Figure 9. Figure 9.

Dose‐response curve for several loop diuretics added to luminal perfusate of isolated rabbit cortical thick ascending limb. Short circuit current (Isc) percentage of control is plotted versus concentration of drug in perfusate. FUR, furosemide; BUM, bumetanide; PIR, piretanide; ETHA, ethacrynic acid; MUZ, muzolimine.

Reproduced from Schlatter et al. 509


Figure 1.

Diagram of nephron depicting major sites of electrolyte and water transport. Closed and open arrows represent active and passive transport processes, respectively.

Reproduced from Puschett 465 with permission


Figure 2.

Chemical structures of diuretic drugs, grouped according to chemical class.



Figure 3.

Effects of four diuretics on generation of solute‐free water (CH2O). Each diagram presents data obtained in single representative study performed in normal human subject undergoing maximal steady‐state water diuresis. In each case, drug was given at arrow. COsm, solute clearance; V, urine flow rate; CNa/Cin × 100, percentage of filtered sodium excreted. U/Posm, urinary and plasma osmolality, respectively. A: Acetazolamide. B: Ethacrynic acid. C: Metolazone. D: Chlorothiazide.

From Puschett 462. From Goldberg 242


Figure 4.

Effects of two diuretic agents on reabsorption of solute‐free water (TCH2O) in three normal human volunteers (M. D., W. M. B., and A. G., respectively) undergoing hypertonic saline diuresis during hydropenic conditions. Drug given during progressive increase in distal delivery of salt and water as indicated by increasing values for solute clearance (COsm). A: Bumetanide, 1 mg intravenously administered at time zero. B: Metolazone, (1 mg intravenously) given at arrows to three subjects (▪, •, ▴, respectively). Same subjects (□, ○, Δ, respectively) were then studied at another time during hypertonic saline infusion, without administration of the diuretic, for comparison purposes.

From Jayakumar and Puschett 311. From Steinmuller and Puschett 549


Figure 5.

Effect of chlorothiazide (CTZ) on proton secretion by turtle bladder. Data indicate that, at each pH level, rates of H+ ion secretion were higher following addition of chlorothiazide (1.0 mg/ml) to mucosal surface.

From Lief et al. 363


Figure 6.

Effects of bumetanide (1 mg intravenously) on urinary pH and absolute excretion rates of titratable acid (UtaV), ammonium ion (+V), and bicarbonate (−V) in representative study in man. Dotted line, time zero; triangles, Uph values.

From Jayakumar and Puschett 311


Figure 7.

Change in percentage of filtered potassium excreted (ΔCk/Cln × 100) as function of increment in percentage of filtered sodium excreted (ΔCNa/Cln × 100) following administration of five diuretic agents to normal human volunteers. Dashed line, zero change from control; ECA, ethacrynic acid.

From Puschett and Rastegar 469


Figure 8.

Main transport systems in various nephron segments. Targets for diuretic actions are indicated by the following symbols: ⊗ Na+‐K+ pump; ○ symport or antiport; conductive pathways. A. proximal tubule; B. thick ascending limb of the loop of Henle; C. distal convoluted tubule; D. collecting duct. See text for further details.

From 394 with permission


Figure 9.

Dose‐response curve for several loop diuretics added to luminal perfusate of isolated rabbit cortical thick ascending limb. Short circuit current (Isc) percentage of control is plotted versus concentration of drug in perfusate. FUR, furosemide; BUM, bumetanide; PIR, piretanide; ETHA, ethacrynic acid; MUZ, muzolimine.

Reproduced from Schlatter et al. 509
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Article Title: Effects of Diuretics on Renal Function
 

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Jules B. Puschett, Joseph Winaver. Effects of Diuretics on Renal Function. Compr Physiol 2011, Supplement 25: Handbook of Physiology, Renal Physiology: 2335-2406. First published in print 1992. doi: 10.1002/cphy.cp080250