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Metabolic acid-base influences on renal thiazide receptor density
D D Fanestil1, D A Vaughn, P Blakely
1Department of Medicine, University of California San Diego, La Jolla 92093-0623, USA.
The American Journal of Physiology
|June 1, 1997
Summary
Metabolic acidosis/alkalosis alters the density of the thiazide-type diuretic receptor (TZR) in the kidney
Area of Science:
- Nephrology
- Renal Physiology
- Molecular Endocrinology
Background:
- Renal regulation of acid-base balance involves multiple nephron segments.
- The distal convoluted tubule (DCT) plays a role in ion transport and acid-base homeostasis.
- Thiazide-type diuretics target the Na-Cl cotransporter in the DCT.
Purpose of the Study:
- To investigate the impact of metabolic acidosis and alkalosis on the distal convoluted tubule (DCT).
- To quantify changes in the density of the thiazide-type diuretic receptor (TZR) in response to acid-base disturbances.
- To correlate TZR density changes with alterations in NaCl reabsorption.
Main Methods:
- Utilized Wistar-Kyoto rats for metabolic acidosis and alkalosis models.
- Administered ammonium chloride (NH4Cl) to induce acidosis and sodium bicarbonate (NaHCO3) to induce alkalosis.
- Quantified renal TZR density using [3H]metolazone binding assays.
Main Results:
- Acidosis significantly decreased TZR density by up to 30% after 7 days.
- Alkalosis significantly increased TZR density by up to 40% within 2-4 days.
- Increased urinary chloride excretion correlated with decreased TZR density during acidosis.
Conclusions:
- Metabolic acidosis decreases renal TZR density, while alkalosis increases it.
- Acid-base disturbances alter TZR density and coordinately affect thiazide-sensitive NaCl reabsorption.
- These adaptive changes in the DCT contribute to regulating distal nephron hydrogen ion secretion.
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