Effects of pyridyl (1,2a) imidazole (Sch 28080) on renal functions in hypokalemic dogs

Abstract

Experiments were conducted to study the effect of H+-K+ATPase inhibitor (Sch 28080) on renal function in hypokalemic dogs. Four groups of animals were used. Group I (n=5), the control dogs (plasma K, 3.4±0.5 mEq/L) received Sch 28080 (10 {u1D707}mol/kg.BW) by intrarenal artrerial injection. Group II (n=5), furosemide-induced hypokalemic dogs (plasma K, 1.7±0.5 mEq/L) received Sch 28080 as in the control group. Group III (n=5), adrenalectomized dogs (plasma K, 3.6±0.2 mEq/L) received Sch 28080 as in the control group. Group IV (n=5), furosemide-induced hypokalemic adrenalectomized dogs (plasma K, 2.2±0.5 mEq/L) were used prior to Sch 28080 administration. It was found that within 40 min of intrarenal arterial injection of Sch 28080 in group I, II and III exhibited significant reductions of the glomerular filtration rate (GFR) by 26%, 34% and 38% respectively and renal plasma flow (ERPF) by 26%, 40% and 51% respectively when compared to the pretreated period. Filtration fraction (FF) of animals in group I,II and III showed no alterations, while renal vascular resistance (RVR) significantly increased by 43%, 124% and 215% respectively. Urine flow rate (V) significantly decreased by 25%, 25% and 32% which coincided with significant decreases of urinary acid excretion by 18%, 24% and 51% in group I, II and III respectively. There were no significant changes of GFR, V and urinary acid excretion in group IV dogs (hypokalemic adrenalectomized dogs) after Sch 28080 administration The ERPF and FF of groups IV dogs showed no significant changes at the first 20 min but at 40 min, ERPF decreased by 28% while FF significantly increased by 62% after given Sch 28080. These results suggest that the inhibitory action of Sch 28080 on H+-K+ATPase depends on either plasma K concentration or adrenal hormone levels (e.g. aldosterone), leading to renal vasoconstricting effect and decrease of urinary acid excretion.