Vasodilatory Effect of Cilnidipine, an L-type and N-type Calcium Channel Blocker, on Rat Kidney Glomerular Arterioles

Abstract

Cilnidipine is a dihydropyridine calcium channel blocker that acts on both L-type and N-type calcium channels. The effects of cilnidipine given intravenously at doses of 2.5, 5.0, and 10 microg/kg were studied using an ex vivo hydronephrosis model in spontaneously hypertensive rats. The effects of nifedipine at a dose of 10 microg/kg were also studied using the same model as a reference. Cilnidipine caused dose-dependent blood pressure reduction and dilatation of the glomerular afferent arterioles; the arteriolar diameter after cilnidipine infusion at 2.5, 5.0, and 10 microg/kg was 101% +/- 3%, 112% +/- 4%, and 123% +/- 6% relative to baseline, respectively. With cilnidipine, dilatation of the efferent arterioles was also observed; it was maximal after 5 to 10 minutes. Five minutes after administration of 2.5, 5.0, and 10 microg/kg of cilnidipine, the efferent arteriolar diameter was 103% +/- 2%, 109% +/- 4%, and 119% +/- 4% of baseline, respectively. This efferent arteriolar dilating action of cilnidipine was abolished after pretreatment with omega-conotoxin, a selective N-type calcium channel blocker. A dose-dependent increase of glomerular blood flow volume was also observed after cilnidipine infusion. Nifedipine, an L-type calcium channel blocker, at a dose of 10 microg/kg reduced systolic blood pressure to a similar extent as cilnidipine at a dose of 10 microg/kg, but only dilated the afferent arterioles and had no significant effect on efferent arterioles. Cilnidipine dilated both the afferent and efferent glomerular arterioles. The efferent arteriolar dilating effect of cilnidipine may be attributed to its inhibition of the N-type calcium channel.