THE EFFECT OF SPECIFIC ANGIOTENSIN RECEPTOR ANTAGONIST LOSARTAN ON DIABETIC NEPHROPATHY IN DIABETIC RAT MODEL

Angiotensin converting enzyme inhibitors prevent the development of diabetic nephropathy by both blocking the renin-angiotensin system and increasing bradykinin levels through inhibition of the kininase II enzyme. Angiotensin receptor antagonists have specific effect on the renin angiotensin system and do not inhibit kininase II enzyme activity. In this study we aimed to investigate the effect of losartan on diabetic nephropathy and to compare it with captopril therapy. Fifty four female Wistar rats, 10-14 weeks old, enrolled in the study. Rats were made diabetic by intraperitoneal injection of streptosotocin in pH 4.5 sodium citrate buffer and did not receive any antidiabetic treatment. Following the first month of injection rats were separated into three groups: The first group received losartan 10 mg/kg via an orogastric catheter, the second group received captopril 50 mg/l in drinking water, and the third one served as the diabetic control group. Twenty four hour urine samples were collected before and after the first mouth of treatment in separate metabolic cages in order to measure urinary albumin, heparan sulphate, and creatinine excretions. Serum glucose and creatinine levels were determined from the blood samples collected via the intracardiac route. The non-diabetic control group consisted of six healthy and age matched female rats. 

Urinary albumin excretion rates were similar at the first month, before the beginning of treatment, among the losartan, captopril, and diabetic control groups (952±689 mg/day, 970±547 mg/day, 910±514 mg/day , respectively). Following the second month urinary albumin excretion rate significantly increased in the control group (1724±945 mg/day, p<0.005). The urinary albumin excretion rates were comparable between losartan and captopril groups, both being significantly lower than that of the control group (778±221 mg/day and 719±341 mg/day, respectively , p<0.05). Urinary heparan sulphate excretion, creatinine clearance and serum creatinine levels were not different among the three groups. In conclusion, losartan prevented the progressive increase in urinary albumin excretion rate in diabetic rats. The effects of losartan and captopril treatment were found to be similar.