The effect of sulfonylurea therapy on defective calcium movement associated with diabetic cardiomyopathy.
Adult rats exposed to 70 mg/kg streptozocin developed characteristic symptoms of overt diabetes, such as muscle wasting and severely elevated blood glucose levels. Chronic treatment of these rats with the sulfonylurea glyburide for a period of 5 weeks did not affect either the weight of the animal or the degree of hyperglycemia. The drug also failed to influence myocardial glucose metabolism. Nevertheless, the decline in myocardial function associated with the diabetic cardiomyopathy was less in the glyburide-treated rats. At higher preload, myocardial work was significantly reduced in the untreated diabetic but was only moderately depressed in the glyburide-treated heart relative to the nondiabetic heart. The improvement in mechanical function was associated with partial recovery of sarcolemmal calcium pump activity. The drug did not alter the initial rate of Na+-Ca2+ exchange, but decreased the capacity of the transport system. The results indicate that glyburide benefits the diabetic heart by a mechanism independent of carbohydrate metabolism.
Mozaffari
M S
MS
Department of Cell Biology and Anatomy, University of Alabama School of Medicine, Birmingham 35294.
Allo
S
S
Schaffer
S W
SW
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000378:metabolism*; D005905:Glyburide / Q000627:therapeutic use; D008297:Male; D009218:Myosins / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000201:enzymology / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
D001786:Blood Glucose; D013453:Sulfonylurea Compounds; D000255:Adenosine Triphosphate; D017301:Ca(2+) Mg(2+)-ATPase; D009218:Myosins; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D005905:Glyburide; D002118:Calcium