Differential effects of the calcium channel blocker nifedipine on renal microcirculation: A comparative study using hydronephrotic rats

Objective: Using a rat in vivo hydronephrotic model we studied the acute an d chronic effects of the short-acting calcium channel blocker nifedipine on renal microcirculation. Background: Antihypertensive drugs such as angiotensin-converting enzyme (A CE) inhibitors that dilate both preglomerular afferent and postglomerular e fferent arterioles are thought to have a renal protective effect; calcium c hannel blockers, in contrast, are thought to elevate glomerular pressure an d aggravate glomerular damage. Because slow-release nifedipine has been sho wn to have beneficial effects on the course of glomerular disease, we hypot hesized that nifedipine has differential effects on renal microcirculation, depending on its mode of action. Methods: Hydronephrosis was induced by permanent ligation of the left urete r in spontaneously hypertensive rats. Under a light microscope, renal micro circulation was observed directly by spreading out the hydronephrotic kidne y as a thin sheet. The effects of nifedipine or imidapril on renal microcir culation were analyzed by importing the microscopic images into a computer. Results: Intravenous injection of nifedipine 10 mu g/kg transiently decreas ed blood pressure and dilated afferent arterioles (from 14% to 19% in diame ter at 10 minutes after injection). In contrast, nifedipine did not affect efferent arteriolar diameter. The ACE inhibitor imidapril 50 mu g/kg was ad ministered in the same manner for reference; it dilated both afferent and e fferent arterioles in this experimental model (17% increase at 20 minutes a nd 12% at 10 minutes, respectively). When administered into an organ bath, nifedipine dilated both afferent (hom 15% to 20% at both 10(-8) M and 10(-6 ) M) and efferent arterioles (15% at 10(-10) M and 20% at 10(-6) M). Conclusions: These results show that when nifedipine is administered to the renal microvasculature in a stable manner, it acts on the renal microcircu lation in the same fashion as do ACE inhibitors.