Effects of efonidipine hydrochloride on the glomerular hemodynamicspp

This study examined direct effects of calcium antagonists on the glomerular hemodynamics. Rabbit afferent (Af-) or efferent arterioles (Ef-Arts) were microperfused in vitro at constant pressure. Ef-Arts were perfused from the distal end of Af-Art through the glomerulus. Increasing doses (10 ^-10 to 10 ^-7M) of nifedipine (Nif), nicardipine (Nic) or efonidipine (Efo) were added into the lumen of Af- or Ef-Arts preconstricted (by about 40%) with norepinephrine. Although Nif and Nic dilated Af-Arts in a dose-dependent manner, they did not cause any dilation in Ef-Arts. In contrast, Efo dilated both Af- and Ef-Arts in a dose-dependent manner ; Efo at 10 ^-7M dilated Af- or Ef-Arts by 71±12% (n=7) or 48±4% (n = 6), respectively. Although Efo's dilator effect on Ef-Art was not affected by inhibiting nitric oxide (NO) or prostaglandin (PG) synthesis (n = 5, respectively), it was significantly attenuated by eliminating the influence of glomerulus (34±3% by Efo at 10 ^-7M, n=5), suggesting that in addition to its direct vasodilator action on Ef-Arts, Efo dilates Ef-Arts partly through glomerulus-derived vasodilator(s) other than NO or PG. These results demonstrate that in addition to dilating Af-Art, Efo but neither Nif nor Nic dilates Ef-Art. Such diverse actions should be taken into consideration when calcium antagonists are used in the treatment of patients with renal dysfunction.