Heme Induction with Delta-Aminolevulinic Acid Stimulates an Increase in Water and Electrolyte Excretion

Abstract

Purpose. Studies were performed to examine hemodynamic and renal function before and after acute induction of the endogenous CO system with delta-aminolevulinic acid (DALA), which drives HO activity. Methods. In vivo studies were conducted on Inactin-anesthetized male Sprague Dawley rats (250–300 g) either with or without chronic pretreatment with L-NAME (50 mg/Kg, q12 hours x4d). Results. DALA (80 μmol/Kg, IV bolus) administration acutely increased endogenous CO production and HO-1 protein. In untreated and L-NAME-pretreated rats, DALA did not alter BP, GFR, or RBF but increased UF, UNaV, and UKV (untreated: Δ108.8 ± 0.28%, 172.1 ± 18.4%, and 165.2 ± 45.9%; pretreated: Δ109.4 ± 0.29%, 187.3 ± 26.9%, and 197.2 ± 45.7%). Acute administration of biliverdin (20 mg/kg, IV) and bilirubin (30 mg/kg, IV) to similarly treated animals did not alter UF, UNaV, and UKV. Conclusion. These results demonstrate that heme oxygenase induction increases urine and electrolyte excretion and suggest a direct tubular action of endogenous carbon monoxide.