Protective effect of cicletanine on renal function in diabetic spontaneously hypertensive rats.

Abstract

Hypertension and diabetes are commonly associated and strongly predispose to renal injuries. In general, antihypertensive therapies protect from these damages, but the effect of cicletanine, a new type of antihypertensive drug, is unknown. This study examines the effects of cicletanine on renal failure in spontaneously hypertensive rats with diabetes (SHRD). Diabetes mellitus was induced with streptozotocin in uninephrectomized SHR. Rats received the vehicle, 10 mg or 50 mg/kg per day of cicletanine for 6 weeks. Age-matched untreated Wistar-Kyoto rats were used as controls. Systolic blood pressure (SBP), microalbuminuria and proteinuria were assessed throughout the treatment. At the end of the study, creatinine clearance measurements and histological analysis of kidneys were performed. Cicletanine did not affect SBP but decreased the elevated albuminuria of diabetic SHR in a dose-dependent manner. Similar results were obtained for proteinuria. Treatment with the high dose of cicletanine also normalized the altered creatinine clearance of diabetic SHR. These results indicate that cicletanine has a renal-protective action, probably blood pressure-independent, in a model combining hypertension and diabetes. The mechanism of renal-protection of cicletanine is not clearly established but may be due to the stimulation of arterial prostacyclin synthesis and/or to the reduction of intraglomerular capillary pressure.

• Authors: M J Duran, S Sennoune, C Arnaud, S Garcia, M T Droy-Lefaix, J M Maixent
• Journal: Cellular and molecular biology (Noisy-le-Grand, France) (Cell Mol Biol (Noisy-le-grand)) Vol. 50 Issue 7 Pg. 869-74 (Nov 2004) ISSN: 0145-5680 [Print] France
• PMID: 15672472 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Protective Agents
• Pyridines
• Creatinine
• cicletanine

Topics

• Albuminuria (drug therapy)
• Animals
• Antihypertensive Agents (pharmacology)
• Blood Pressure
• Body Weight (drug effects)
• Creatinine (blood, urine)
• Diabetes Mellitus, Experimental (drug therapy, physiopathology)
• Dose-Response Relationship, Drug
• Kidney (drug effects, pathology)
• Male
• Nephrectomy
• Protective Agents (therapeutic use)
• Proteinuria
• Pyridines (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY