Correlation between decrease of 11beta-hydroxysteroid dehydrogenase activity and hypokalemia induced by furosemide in rats
Abstract
Aim: To investigate the correlation between decrease of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity and hypokalemia induced by furosemide (Fur) in rats.
Methods: SD rats were given single dose or successive doses of Fur by gavage. The activity of 11beta-HSD was evaluated by measuring the ratio of 11-dehydrocorticosterone (A) and corticosterone (B) in urine and conversion rate of B to A in renal cortex microsome preparation was determined with HPLC.
Results: After giving single dose of Fur (40, 100, and 250 mg/kg) or multiple doses of Fur (10, 20, and 100 mg/kg, bid x 20 d), the ratio of A/B was reduced by 29.0 %, 58.6 %, and 60.9 % at 0 - 2 h; 14.4 %, 36.0 %, and 44.9 %, respectively; the conversion rate of B to A was decreased by 29 %, 33 %, and 37 %; 6 %, 17 %, and 23 %, respectively. The serum potassium was significantly reduced by multiple doses of Fur (20 and 100 mg/kg, bid x 20 d) (P < 0.01). The reduction in serum potassium was positively correlated with the lowering of A/B ratio and the conversion of B to A (P < 0.01).
Conclusion: The inhibition of renal 11beta-HSD activity may be another new biochemical mechanism for hypokalemia induced by Fur.
Keywords:
Methods: SD rats were given single dose or successive doses of Fur by gavage. The activity of 11beta-HSD was evaluated by measuring the ratio of 11-dehydrocorticosterone (A) and corticosterone (B) in urine and conversion rate of B to A in renal cortex microsome preparation was determined with HPLC.
Results: After giving single dose of Fur (40, 100, and 250 mg/kg) or multiple doses of Fur (10, 20, and 100 mg/kg, bid x 20 d), the ratio of A/B was reduced by 29.0 %, 58.6 %, and 60.9 % at 0 - 2 h; 14.4 %, 36.0 %, and 44.9 %, respectively; the conversion rate of B to A was decreased by 29 %, 33 %, and 37 %; 6 %, 17 %, and 23 %, respectively. The serum potassium was significantly reduced by multiple doses of Fur (20 and 100 mg/kg, bid x 20 d) (P < 0.01). The reduction in serum potassium was positively correlated with the lowering of A/B ratio and the conversion of B to A (P < 0.01).
Conclusion: The inhibition of renal 11beta-HSD activity may be another new biochemical mechanism for hypokalemia induced by Fur.