title: Divergent renal vasodilator action of L- and T-type calcium antagonists in vivo.
abstract: OBJECTIVE
  To assess the in-vivo action on the renal microvasculature of the calcium antagonists nifedipine (L-type blocker), efonidipine (L/T-type blocker), and mibefradil (predominant T-type blocker).
  
  
  METHODS
  An intravital needle-type charge-coupled device (CCD) camera videomicroscope was introduced to visualize the renal microcirculation directly in vivo.
  
  
  METHODS
  In anesthetized mongrel dogs, nifedipine (0.01-1 mg/kg per min), efonidipine (0.033-0.33 mg/kg per min), or mibefradil (0.01-1 mg/kg per min) was infused intravenously after the insertion of a CCD probe into the kidney. Renal microvascular responses to calcium antagonists were directly evaluated, with concomitant observation of renal clearance.
  
  
  RESULTS
  Each calcium antagonist caused modest vasodepressor action without affecting heart rate. Nifedipine (1 mg/kg per min, n = 9) increased renal plasma flow (RPF) (14 +/- 4%, P < 0.05) and glomerular filtration rate (GFR) (19 +/- 5%, P < 0.05), and tended to increase the filtration fraction (5 +/- 2% increment, P = 0.07). Efonidipine (0.33 mg/kg per min, n = 9), however, had no effect on filtration fraction, with 14 +/- 6% increments in RPF (P < 0.05) and 14 +/- 7% increments in GFR (P = 0.08). Rather, mibefradil (1 mg/kg per min, n = 9) elicited 6 +/- 2% decreases in filtration fraction (P < 0.05), with slight increments in RPF (6 +/- 3%) and no changes in GFR. In direct in-vivo microvasculature observations, nifedipine caused predominant (22 +/- 2%) dilatation of afferent arterioles (from 15.5 +/- 0.4 to 18.9 +/- 0.4 microm, n = 5), compared with that of efferent arterioles (10 +/- 2%; from 11.0 +/- 0.4 to 12.1 +/- 0.3 microm). In contrast, efonidipine caused a similar magnitude of vasodilatation (16 +/- 4%) compared with 18 +/- 2%; n = 6), and mibefradil caused greater dilatation of efferent arterioles (20 +/- 4%, n = 7) than that of afferent arterioles (13 +/- 4%).
  
  
  CONCLUSIONS
  There exists marked heterogeneity in action of nifedipine, efonidipine and mibefradil on the renal microvascular in canine kidneys in vivo. Furthermore, our current observations suggest an important contribution of T-type calcium channel activity to efferent arteriolar tone in vivo.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.forename: E
authors.initials: E
authors.lastname: Kubota
authors.forename: H
authors.initials: H
authors.lastname: Tokuyama
authors.forename: K
authors.initials: K
authors.lastname: Okubo
authors.forename: I
authors.initials: I
authors.lastname: Takamatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Ozawa
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D020748:Mibefradil / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D020748:Mibefradil; C066425:efonidipine; D009543:Nifedipine