Sj. Humphrey, EFFECTS OF K-ATP BLOCKING GUANIDINE DIURETICS DURING EXPERIMENTAL KALIURESIS IN RATS AND DOGS, Methods and findings in experimental and clinical pharmacology, 17(8), 1995, pp. 519-528
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+ excret
ion 3-fold. This kaliuresis was further enhanced by oral diuretic dose
s 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 kaliur
esis induced by oral isotonic saline (200 mL), oral KCl (30.8 mEq), su
bcutaneous deoxycorticosterone acetate (1.0 mg/kg), and oral acetazola
mide (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 rela
tively eukalemic diuresis under normal and high K+ excretion condition
s, and their putative renal tubular K-ATP blocking action seems an eff
ective means of inducing diuresis with less k(+) imbalance than with s
tandard diuretics.