An Exploratory Study on the Development of Drug-induced Renal Hyperpotassemia in General Anesthetized Rats

Abstract

Management of hyperpotassemia is important in a perioperative period. Decreased renal-potassium excretion is a major mechanism of hyperpotassemia. However, current therapeutics for renal hyperpotassemia are not specific to the target site. Thus, we develop an animal model of renal hyperpotassemia for use in evaluation of candidate drugs. Nine-week-old male Wistar-Imamichi rats were intubated after anesthesia and attached to a ventilator. Heart rate and arterial blood pressure were continuously measured. After continuous infusion (c.i.) of normal saline for 30 min amiloride was given bolus infusion (36 μg/kg) followed by c.i. of KCl (0.3, 0.6, 0.9 mmol/kg) and amiloride (10.8 μg/kg) for 75 min. Blood pH was measured before and after co-administration of KCl and amiloride. Serum potassium concentration and urinary potassium excretion were measured every 15 min by collecting arterial blood and urine via indwelling catheters. Changes in serum potassium concentration from a value immediately before the co-administration of KCl and amiloride were expressed as Δpotassium. An increase in the Δpotassium was dose-dependent and greater in the KCl 0.6 and KCl 0.9 compared with the control (P = 0.024, 0.0003, respectively). It was also greater in the KCl 0.6 and amiloride than KCl 0.6 (P = 0.016). The blood pH was not changed among the groups. Blood pressures and heart rates tended to decrease, and urine volume tended to increase in all groups. In conclusions, we developed a renal hyperpotassemia model in the general anesthetized rats with a stable pH which could minimize potassium fluctuations. This model can be applied for evaluation of the candidate drugs for renal hyperpotassemia.