Effects of troglitazone and temocapril in spontaneously hypertensive rats with chronic renal failure

Objective The insulin resistance state is common in humans and animals with chronic renal failure. We investigated the effects of troglitazone, an ins ulin sensitizer, on blood pressure and nephropathy in the remnant kidney mo del of spontaneously hypertensive rats (SHR). Methods Eight-week-old male SHR were subjected to five-sixth nephrectomy, A t the age of 10 weeks, the rats were randomly allocated to groups that rece ived troglitazone (70 mg/kg per day); the angiotensin converting enzyme inh ibitor temocapril (10 mg/kg per day); troglitazone (70 mg/kg per day) plus temocapril (10 mg/kg per day), or a vehicle alone as an untreated control g roup. Systolic blood pressure (SBP) and urinary protein excretion were meas ured every 2 weeks. At the age of 22 weeks, biochemical measurements and hi stological examination were performed. Results Blood glucose, glycosylated hemoglobin and body weight were similar in the four groups. SEP, serum creatinine and glomerular sclerosis index w ere significantly reduced in all treated groups compared with those in the control group. Urinary protein excretion, glomerular volume and aortic medi a thickness were significantly decreased in temocapril-treated rats and tro glitazone plus temocapril-treated rats compared with those in control rats. Although antihypertensive effects of troglitazone were minute compared wit h those of temocapril or troglitazone plus temocapril, there was no signifi cant difference between the glomerular sclerosis indices in these three dru g-treated groups. Conclusions The results suggest that troglitazone has renoprotective effect s in this rat model. These effects might be due to the inhibition of growth factors rather than to the minute hypotensive effect, although the mechani sm remains to be elucidated. I Hypertens 19:503-510 (C) 2001 Lippincott Wil liams & Wilkins.