title: Effects of an N-type calcium antagonist on angiotensin II-renin feedback.
abstract: BACKGROUND
  Interrupting the renin-angiotensin system (RAS) with an angiotensin II receptor blocker (ARB) has been found to induce RAS overactivation. In this study, we investigated the effect of 2 calcium channel blockers (CCBs), cilnidipine (L-/N-type CCB) and amlodipine (L-type CCB), on the RAS activation induced by an ARB in a strain of spontaneously hypertensive rats (SHR/Izm, 10 weeks of age).
  
  
  METHODS
  Rats intravenously catheterized for blood collection were randomly divided into groups that were administered the vehicle, the ARB valsartan or valsartan combined with one of the 2 CCBs. Their blood and kidneys were collected 270 min after administration.
  
  
  RESULTS
  Valsartan increased the plasma angiotensin II (Ang II) level in a dose-dependent manner. Cilnidipine suppressed the increase in plasma renin activity and plasma Ang II levels induced by valsartan, but amlodipine did not. Combined administration of cilnidipine, but not amlodipine, and valsartan significantly reduced the noradrenaline content in the renal cortex.
  
  
  CONCLUSIONS
  The results of this study suggest that the suppressive effect of cilnidipine on the valsartan-induced increase in RAS activity can be partly explained by its sympatholytic action mediated by N-type calcium channel blockade, and that combined administration of cilnidipine and valsartan might provide a synergistic therapeutic effect.
authors.affiliation: Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Aritomi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Niinuma
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ogawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Konda
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000737:chemistry*; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008954:Models, Biological; D051381:Rats; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D013777:Tetrazoles; D000804:Angiotensin II; D017311:Amlodipine; D000068756:Valsartan; C065927:cilnidipine; D012083:Renin; D014633:Valine