EFFECTS OF CHRONIC TREATMENT WITH CROMAKALIM AND GLIBENCLAMIDE IN ALLOXAN-INDUCED DIABETIC RATS

• Published in: Pharmacological research 2002-08, Vol.46 (2), p.101-105
• Main Authors: KULKARNI, JAYANT S., METHA, ANITA A., SANTANI, DEV D., GOYAL, RAMESH K.
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive Agents - therapeutic use; Blood Glucose - analysis; Blood Pressure - drug effects; Cromakalim - therapeutic use; diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Drug Interactions; Female; Glyburide - therapeutic use; Heart Rate - drug effects; Hypertension - complications; Hypertension - drug therapy; Hypoglycemic Agents - therapeutic use; potassium channels; Rats; Rats, Wistar; thyroid hormone
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/S1043-6618(02)00078-6

We have studied the effects of chronic treatment with cromakalim (75 ug kg −1 per day) and glibenclamide (20 mg kg −1 per day) in alloxan-induced diabetic rats. Injection of alloxan (60 mg kg −1/i.v., single dose) produced a significant increase in the blood pressure, bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism and depression in left ventricular developed pressure (LVDP). While glibenclamide significantly prevented alloxan-induced hyperglycemia and hypoinsulinaemia, it failed to alter hypertension, bradycardia, hypertriglyceridaemia and hypercholesterolemia. Treatment with cromakalim-prevented hypertension and bradycardia, but not the hyperglycemia or hypoinsulinaemia. Co-administration of cromakalim with glibenclamide antagonized the effect of glibenclamide on these parameters. Cromakalim treatment also prevented alloxan-induced hypercholesterolemia and hypertriglyceridaemia. It also produced a significant increase in serum T 3 and T 4 levels. Glibenclamide did not significantly alter alloxan-induced hypothyroidism. In conclusion our data suggest that cromakalim and glibenclamide produce some metabolic effects that are either not related to K ATP channel modulation or may involve different sub-types of potassium channels. Further glibenclamide when combined with cromakalim may not be beneficial in a condition when diabetes mellitus and hypertension co-exits.