Effects of chronic treatment with cromakalim and glibenclamide in alloxan-induced diabetic rats.
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.
Kulkarni
Jayant S
JS
Cadila Pharmaceuticals, Dholka, Ahmedabad 387810, India.
Metha
Anita A
AA
Santani
Dev D
DD
Goyal
Ramesh K
RK
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D019806:Cromakalim / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D019806:Cromakalim; D005905:Glyburide