Effects of chronic combined treatment with captopril and pravastatin on the progression of insulin resistance and cardiovascular alterations in an experimental model of obesity in dogs.
Obesity is a metabolic disorder in which multiple clinical and biochemical alterations coexist. However, the progression of these alterations in relation to weight gain has not been investigated in detail. Therefore, we studied the evolution of insulin resistance and associated risk factors in a model of experimental obesity in dogs. We also studied whether chronic exposure to these pathogenic factors could induce cardiac and vascular alterations. Twenty male age- and body weight-matched beagle dogs were divided into four groups (n = 5), according to diet and pharmacologic therapy received, and followed for 2 years. Control animals were maintained with a regular diet, while the 15 remaining animals were fed a high-fat diet. The Obese group of dogs received no therapy, whereas the Capto group received 25 mg/12 h captopril, and the Prava+Capto was treated with 10 mg/24 h pravastatin plus the same dose of captopril throughout the study. Periodical determinations of clinical and biochemical parameters were made, and the degree of insulin resistance was also estimated. After the 2-year follow-up, the dogs were killed and vascular thickening in the aorta and the coronary arteries was evaluated. In addition, cardiac hypertrophy was estimated by heart weight and free-wall left ventricular width. Chronic pravastatin plus captopril treatment, together with decreasing weight gain rate, ameliorated the progression of insulin resistance and associated risk factors (hyperinsulinemia, hypercholesterolemia) related to this severe model. In addition, this combined therapy showed cardioprotective action, as cardiac and vascular hypertrophy observed in the Obese group was prevented. These positive results seems to emerge from the synergistic effects of both drugs, as captopril as monotherapy induced only a slight benefit on these parameters.
Department of Endocrinology, Hospital Ramón y Cajal, Universidad Alcalá de Henares, Madrid, Spain.
E
E
Villa
A
A
Rábano
O G
OG
Albarrán
L M
LM
Ruilope
R
R
García-Robles
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D004359:Drug Therapy, Combination; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017035:Pravastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D002784:Cholesterol; D002216:Captopril; D017035:Pravastatin