Effects of K-ATP blocking guanidine diuretics during experimental kaliuresis in rats and dogs

Several guanidine diuretics related to the renal tubular K-ATP blocker U-37883A were compared to standard diuretics under high K+ excretion conditions. In conscious rats, oral KCl(0.28 mEq) increased K+ excretion 3-fold. This kaliuresis was further enhanced by oral diuretic doses of ethoxzolamide (1 and 2 mg/kg), hydrochlorothiazide (HCTZ; 0.3 and 0.9 mg/kg), and furosemide (18 mg/kg), but was significantly blunted by oral triamterene (1 and 10 mg/kg). By comparison, diuretic doses of U-37883A and analogs U-18177 (10 and 30 mg/kg) and U-38658A (3 and 9 mg/kg) did not affect K+ excretion. In conscious dogs, oral U-18177A (10 mg/kg) and HCTZ (1 mg/kg) were compared during 3- to 13-fold kaliuresis induced by oral isotonic saline (200 mL), oral KCl (30.8 mEq), subcutaneous deoxycorticosterone acetate (1.0 mg/kg), and oral acetazolamide (20 mg/kg). HCTZ was diuretic and further increased K+ excretion and its fractional clearance by 42 and 34%, respectively. Conversely, U-18177A was diuretic and slightly reduced these kaliuretic parameters by 11 and 20%. Thus, the guanidines U-18177 and U-37883A exert a relatively eukalemic diuresis under normal and high K+ excretion conditions, and their putative renal tubular K-ATP blocking action seems an effective means of inducing diuretics with less K+ imbalance than with standard diuretics.