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 biochem ical alterations coexist. However, the progression of these alteration s in relation to weight gain has not been investigated in detail. Ther efore, we studied the evolution of insulin resistance and associated r isk factors in a model of experimental obesity in dogs. We also studie d whether chronic exposure to these pathogenic factors could induce ca rdiac and vascular alterations. Twenty male age- and body weight-match ed beagle dogs were divided into four groups (n = 5), according to die t and pharmacologic therapy received, and followed for 2 years. Contro l 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 th e Prava + Capto was treated with 10 mg/24 h pravastatin plus the same dose of captopril throughout the study. Periodical determinations of c linical and biochemical parameters were made, and the degree of insuli n resistance was also estimated. After the 2-year follow-up, the dogs were killed and vascular thickening in the aorta and the coronary arte ries 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 sever e model. In addition, this combined therapy showed cardioprotective ac tion, as cardiac and vascular hypertrophy observed in the Obese group was prevented. These positive results seems to emerge from the synergi stic effects of both drugs, as captopril as monotherapy induced only a slight benefit on these parameters. Am J Hypertens 1998;11:844-851 (C ) 1998 American Journal of Hypertension, Ltd.