Effect of bis-1,4-dihydropyridine in the kidney of diabetic rats

The in vivo effectiveness of 4-dihydropyridine (bis-1,4-dhp),a new calcium-channel blocker,as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. diabetes in male wistar rats,control,diabetic,control + bis-1,4-dhp,and diabetic + bis-1,4-dhp,was induced by a single administration of stz (55 mg.kg-1,i.p.). in the drug-treated groups,treatment with bis-1,4-dhp (10 mg.kg-1.day-1) started one week before diabetes induction; bis-1,4-dhp was dissolved in dmso (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). parameters evaluated were body weight,blood glucose,albuminuria,proteinuria,creatinine,urea excretion,kidney's weight / body weight ratio,and kidney perfusion pressure in all rat groups at different times of diabetes (2,4,6,and 10 weeks). kidney weight of diabetic rats significantly increased vs. control,control + bis-1,4-dhp,and diabetic + bis-1,4-dhp rats at different times of diabetes. the ratios % kidney weight / 100 g body weight were different between control,control + bis-1,4- dhp,and diabetic + bis-1,4-dhp rats vs. diabetic rats (p < 0.05). kidney perfusion pressure was decreased by diabetes,while it was partially recovered by bis-1,4-dhp treatment in response to phenylephrine. bis-1,4-dhp had a tendency to decrease hyperglycemia vs. diabetic rats,even though glycemia was too high as compared with controls,and it ameliorated albuminuria,creatinine,and urea excretion,suggesting a favorable effect on renal haemodynamics. bis-1,4- dhp,by inhibiting ca2+ entrance,induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction,but does not have significant impact on hyperglycemia. © 2013 the japanese pharmacological society.