Effect of the two new calcium channel blockers mebudipine and dibudipine on vascular flow of isolated kidney of normal and diabetic rats

Background and aims: Calcium channel blockers (CCBs) are powerful drugs in the treatment of hypertension. These agents also preserve or improve renal function in patients with essential hypertensive renal disease or diabetic renal disease. There is increasing experimental evidence for the beneficial effects of dihydropyridine-type CCBs. In previous researches mebudipine and dibudipine two newly synthesized CCBs, improved normal rat kidney perfusion. The study was designed to investigate the effects of these new drugs on vascular flow of isolated kidney from diabetic rats comparing to nifedipine, also to test that the effects of the new DHPs and nifedipine on renal blood flow in the isolated perfused kidney might be altered in experimental diabetic rats. Methods: In this study normal and STZ-induced 6- to 7-week diabetic rats were used. Following the establishment of renal perfusion with a constant baseline pressure of 85–95 mmHg, the renal vasculature was constricted by phenylephrine (PE) injection. Changes in the baseline perfusion pressure were recorded. Then DHP CCBs prepared in perfusion medium was fed to the kidney for 30 min. Finally alterations in the baseline pressure arising from PE administrations in the presence of DHPs were recorded and data analyses were done. Results: Mebudipine and dibudipine (1–10 μM) were more effective in the inhibition of phenylephrine (PE)-induced perfusion pressure in isolated kidney of diabetic rats compared to nifedipine at similar concentrations. Based on the obtained EC50 values for DHPs-induced inhibition of prefusion pressure, it is referred that lower concentrations of mebudipine and dibudipine are needed to inhibit PE-evoked increments of renal perfusion pressure in diabetic rats. Conclusion: Mebudipine and dibudipine have more potency in inhibiting PE-elicited perfusion pressure in isolated kidney from diabetic rats compared to normal rats.