Investigation into the cardiac effects of spironolactone in the experimental model of type 1 diabetes.
We have studied the effect of 8-week treatment with spironolactone (20 mg*kg(-1)*day(-1)) on cardiovascular complications associated with streptozotocin (STZ)-diabetic rats. Wistar rats were made diabetic with STZ (45 mg/kg, intravenously). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzyme, and C-reactive protein levels; reduction in heart rate; and cardiac hypertrophy. Chronic treatment with spironolactone significantly prevented STZ-induced bradycardia, hypertension, and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly reduced the elevated cholesterol, very-low-density lipoprotein, and triglyceride levels and increased the lower high-density lipoprotein-cholesterol levels in diabetic rats. Furthermore, spironolactone also produced a significant reduction in the elevated creatinine levels, C-reactive protein, and levels of lactate dehydrogenase and creatinine kinase. It also produced beneficial effect in diabetic rats by preventing cardiac hypertrophy as evident from decrease in left ventricular collagen levels, cardiac hypertrophy index, and left ventricular hypertrophy index. Our data suggest that spironolactone prevents not only the STZ-induced metabolic abnormalities but also cardiovascular complications.
Goyal
Bhoomika R
BR
Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India.
Solanki
Nilay
N
Goyal
Ramesh K
RK
Mehta
Anita A
AA
D000818:Animals; D001769:Blood / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002352:Carrier Proteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D048909:Diabetes Complications / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D007328:Insulin / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*; D013311:Streptozocin / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002352:Carrier Proteins; C030929:Crp protein, rat; D007328:Insulin; D008074:Lipoproteins; D014280:Triglycerides; D013148:Spironolactone; D013311:Streptozocin; D003094:Collagen; D002784:Cholesterol; D003404:Creatinine; D003402:Creatine Kinase