Acetazolamide Causes Renal HCO3 ‾ Wasting but Inhibits Ammoniagenesis and Prevents the Correction of Metabolic Acidosis by the Kidney.

Acetazolamide Causes Renal HCO3‾ Wasting but Inhibits Ammoniagenesis and Prevents the Correction of Metabolic Acidosis by the Kidney. Am J Physiol Renal Physiol. 2020 Jul 13;: Authors: Alam P, Amlal S, Thakar CV, Amlal H Abstract Carbonic anhydrase (CAII) binds to the basolateral Na+: HCO3‾ cotransporter (NBCe1) and facilitates HCO3‾ reabsorption across the proximal tubule. However, whether the inhibition of CAII with acetazolamide (ACTZ) alters NBCe1 activity and interferes with ammoniagenesis pathway remains elusive. To address this issue, we compared the renal adaptation of rats treated with ACTZ vs. NH4Cl loading for up to 2 weeks. The results indicate that ACTZ-treated rats exhibited a sustained metabolic acidosis for up to 2 weeks, whereas in NH4Cl loaded rats, metabolic acidosis was corrected within 2 weeks of treatment. NH4+ excretion increased by 10-fold in NH4Cl loaded rats but only slightly (1.7-flod) in ACTZ-treated rats during the first week despite similar degree of acidosis. Immunoblotting studies showed that the protein abundance of GA (4-fold), GDH (6-fold) and SN1 (8-fold) increased significantly in NH4Cl loaded rats, but remained unchanged in ACTZ-treated animals. NHE3 and NBCe1 proteins were upregulated in response to NH4Cl loading but not to ACTZ treatment and were rather sharply downregulated after 2 weeks of ACTZ treatment. ACTZ causes renal HCO3‾ wasting and induces metabolic acidosis, but inhibits the...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research