title: Amlodipine and benazeprilat differently affect the responses to endothelin-1 and bradykinin in porcine ciliary arteries: effects of a low and high dose combination.
abstract: OBJECTIVE
  Visual field defects caused by vasospasm are often encountered in ophthalmology as a feature of glaucoma with poor response to conventional treatment. Combination therapy with drugs acting via different mechanisms might be more effective. Therefore, the effects of the calcium antagonist amlodipine and the angiotensin converting enzyme (ACE) inhibitor benazeprilat at low and high dose combination on contractions to endothelin-1 and endothelium-dependent relaxations to bradykinin were examined in porcine ciliary arteries.
  
  
  METHODS
  Segments of the arteries were suspended in myographs for isometric tension recording.
  
  
  RESULTS
  Pretreatment of the vessels with either amlodipine, the low or high dose combination significantly reduced the sensitivity to endothelin-1 as compared to control (concentration shift 18.3-fold, 14.2-fold, 23.3-fold respectively; p < 0.05), while benazeprilat was ineffective. The maximal response to endothelin-1 (10(-7) M) was most inhibited by the high dose combination which reduced the contractions by 49% as compared to control (p < 0.05). The low dose combination and amlodipine alone were less effective (reduction: 25%; p < 0.05 and 20%; n.s., respectively). On the other hand, benazeprilat enhanced the sensitivity (concentration shift 73-fold; p < 0.05) and maximal relaxation to bradykinin (by 27%; p < 0.01), whereas amlodipine or the low or high dose combination were ineffective.
  
  
  CONCLUSIONS
  These findings indicate that amlodipine and benazeprilat differently affect vascular function of ciliary arteries. A high dose combination of both substances was most effective in inhibiting contractions to endothelin-1, suggesting a potentiating effect of the two compounds. In contrast, endothelium-dependent relaxations to bradykinin were enhanced by benazeprilat alone, but not when combined with amlodipine.
authors.affiliation: Department of Research, University Hospital Basel, Switzerland.
authors.forename: M G
authors.initials: MG
authors.lastname: Lang
authors.forename: P
authors.initials: P
authors.lastname: Zhu
authors.forename: P
authors.initials: P
authors.lastname: Meyer
authors.forename: G
authors.initials: G
authors.lastname: Noll
authors.forename: I O
authors.initials: IO
authors.lastname: Haefliger
authors.forename: J
authors.initials: J
authors.lastname: Flammer
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002924:Ciliary Body / Q000098:blood supply / Q000187:drug effects*; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D005901:Glaucoma; D013552:Swine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D002121:Calcium Channel Blockers; D019332:Endothelin-1; D017311:Amlodipine; C052133:benazeprilat; D001920:Bradykinin