Effects of combined therapy of ACE inhibitor and exercise on the development of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rats

Our previous studies used type-2 diabetic model Otsuka Long-Evans Tokushima fatty (OLETF) rats, and showed that both exercise and diet regimen decreased body weight (BW) and improved glucose intolerance (GI), and dyslipidemia. However, exercise regimenwas also associated with increased blood pressure (BP), diabetic nephropathy (DN) progression characterized by an increase in urinary albumin excretion (UAlb), and morphological abnormalities of the kidneys. This study examined the effects of an exercise regimen alone and the combined treatment of exercise and an antihypertensive medication, captopril (Capt), on systemic BP, DN progression, BW, GI, and dyslipidemia in OLETF rats. Twenty-four male OLETF rats were divided into the following groups: voluntary exercise alone (OLETF-Ex), Capt administration alone (OLETF-Capt), Capt and exercise (OLETF-Capt & Ex), and sedentary control (OLETF-Sed) groups. Six male Long-Evans Tokushima Otsuka (LETO) rats were used as a normal sedentary control (LETO-Sed). These treatments were conducted from 21 to 30 weeks of age. Approximately 20 mg/kg/day of Capt was administered daily. After the treatment, the OLETF-Ex group experienced decreased BW and improved GI and dyslipidemia; however, it was associated with diastolic BP elevation and DN progression. The OLETF-Capt group experienced decreased BP and serum TG concentration and inhibited DN progression. The OLETF-Capt & Ex group experienced decreased BW and BP, and improved GI and dyslipidemia without the progression of DN. This study demonstrated that a combined treatment of exercise and antihypertensive agents, such as Capt, is recommended as an ideal regimen for hypertensive diabetic patients in the pre-nephropathy stage to avoid DN progression induced by an exercise regimen alone.