DIVERSE EFFECTS OF CALCIUM-ANTAGONISTS ON GLOMERULAR HEMODYNAMICS

This study examined the direct effects of calcium antagonists on glome rular hemodynamics. Rabbit afferent (Af-) or efferent arterioles (Ef-A rts) were microperfused in vitro at constant pressure. Ef-Arts were pe rfused from the distal end of Af-Art through the glomerulus. Increasin g doses (10(-10) to 10(-7) M) of nifedipine (Nif), nicardipine (Nic) o r manidipine (Man) were added into the lumen of Af- or Ef-Arts precons tricted (by about 40%) with norepinephrine. Although Nif and Nic dilat ed Af-Arts in a dose-dependent manner, they did not cause any dilation in Ef-Arts. In contrast, Man dilated both Af- and Ef-Arts in a dose d ependent manner; Man at 10(-7) M dilated Af- and Ef-Arts by 71 +/- 12% (N = 7) and 38 +/- 3% (N = 6), respectively. Although Man's dilator e ffect on Ef-Art was not affected by inhibiting nitric oxide (NO) synth esis (N = 6), it was markedly attenuated by eliminating the influence of glomerulus (14 +/- 3% by Man at 10(-7) M, N = 5). These results dem onstrate that in addition to dilating Af-Art, Man, but not Nif or Nic, dilates Ef-Art through a glomerulus-derived vasodilator(s) other than NO. Such diverse actions should be taken into consideration when calc ium antagonists are used in the treatment of patients with cardiovascu lar and renal diseases.