Evaluation of the potassium channel activator levcromakalim (BRL38227) on the lipid profile, electrolytes and blood glucose levels of streptozotocin-diabetic rats.

Levcromakalim is a vasorelaxant used in the management of hypertension in diabetes mellitus. Thus, the effects of levcromakalim were investigated in streptozotocin (STZ)-diabetic rats. Diabetes was induced in Wistar albino rats with a single injection of STZ (60 mg/kg, i.p.) following chronic (4 weeks) treatment with levcromakalim (75 μg/kg per day). Rats were then divided into the following groups (n = 5 in each group): (i) a normal saline (2 mL/kg)-treated group; (ii) a 5 mg/kg glibenclamide-treated group; (iii) 350 mg/kg metformin-treated group; and (iv) 5, 10, 20 and 40 IU/kg insulin-treated groups. Rats were transferred to metabolic cages and the lipid profile, plasma and urine electrolytes and blood glucose levels were determined 24 h after drug administration. Levcromakalim treatment significantly reduced total cholesterol, low-density lipoprotein (LDL), and triglyceride levels in diabetic rats (all P < 0.05 compared with untreated diabetic rats). In addition, levcromakalim reduced plasma sodium, bicarbonate, and chloride levels, but increased urinary bicarbonate and chloride levels, in diabetic rats (all P < 0.05 compared with untreated diabetic rats). Levcromakalim significantly inhibited the effects of glibenclamide, metformin, and low-dose (20 IU/kg) insulin treatment in diabetic rats (all P < 0.05). Only 40 IU/kg insulin produced significant reductions in hyperglycemia in levcromakalim-treated diabetic rats. Levcromakalim induced resistance to glibenclamide, metformin, and low-dose insulin treatment in diabetic rats, leading to persistent hyperglycemia. However, reductions in LDL, total cholesterol and triglyceride levels following chronic levcromokalim treatment may decrease the risk of cardiovascular disease in diabetic rats.