Renal-protective effect of nondepressor dose of cicletanine in diabetic rats with hypertension

We assessed the renal and cardiac benefits of cicletanine (CIC), a furopyri dine derivative drug with diuretic and antihypertensive properties, in diab etic spontaneously hypertensive rats with renal impairment. Uninephrectomiz ed streptozotocin (STZ)-diabetic spontaneously hypertensive Izmo rats (SHBI zm) (10 weeks old) were randomly assigned to receive vehicle or CIC (100 mg /kg/day, orally), and age-matched, uninephrectomized STZ diabetic Wistar-Ky oto Izmo rats (WKYIzm) were assigned to receive vehicle for up to 12 weeks. Blood pressure increased progressively in diabetic SHBIzm but not in diabe tic WKYIzm. Urinary albumin excretion increased significantly in both diabe tic SHRIzm and diabetic WKYIzm throughout the experiment. The antihypertens ive effect of CIC was not significantly observed in diabetic SHRIzm. Howeve r, the subdepressor doses of CIC significantly decreased urinary albumin ex cretion serum creatinine, and blood. urea nitrogen in diabetic SHRIzm. Thes e results were confirmed by morphological analysis of kidneys in each group of rats. The index of focal glomerular sclerosis (FGS) in diabetic SHRIzm was significantly higher than that in diabetic WKYIzm. The GIC treatment si gnificantly and effectively protected against an increase in the index of F GS in diabetic SHRIzm. Moreover, CIC treatment significantly attenuated the increase in the heart weight to body weight. ratio in diabetic SHRIzm. Tre atment with CIC did not affect urinary and blood glucose concentrations at this dose. These results suggest that CIC has a renal-protective action, wh ich is not related to improvement of diabetes or improvement of high blood pressure in diabetic rats with hypertension. The action might be due to the reduction of intraglomerular capillary pressure or protection of the renal glomerular vascular endothelial cell injury and mesangial cell injury thro ugh stimulation of PGI(2) generation or elimination of free radicals, altho ugh the mechanism remains to be further investigated, Am J Hypertens 2000; 13:298-306 (C) 2000 American Journal of Hypertension Ltd.