Diverse effects of calcium antagonists on glomerular hemodynamics.
This study examined the direct effects of calcium antagonists on 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(-7) M) of nifedipine (Nif), nicardipine (Nic) or manidipine (Man) 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, Man dilated both Af- and Ef-Arts in a dose dependent 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 effect on Ef-Art was not affected by inhibiting nitric oxide (NO) synthesis (N = 6), it was markedly attenuated by eliminating the influence of glomerulus (14 +/- 3% by Man at 10(-7) M, N = 5). These results demonstrate 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 calcium antagonists are used in the treatment of patients with cardiovascular and renal diseases.
Arima
S
S
Department of Clinical Biology and Hormonal Regulation, Tohoku University School of Medicine, Sendai, Japan.
Ito
S
S
Omata
K
K
Tsunoda
K
K
Yaoita
H
H
Abe
K
K
D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010477:Perfusion; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester