title: The vasodilating effect of acetazolamide and dorzolamide involves mechanisms other than carbonic anhydrase inhibition.
abstract: OBJECTIVE
  Carbonic anhydrase inhibitors reduce intraocular pressure, which may protect the optic nerve from ischemia. However, carbonic anhydrase inhibitors have also been shown to dilate the blood vessels in the retina and the optic nerve head. The purpose of the present study was to investigate whether CO(2), H(+), or factors other than carbonic anhydrase inhibition are involved in this vasodilating effect.
  
  
  METHODS
  Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph for isometric force measurements. After precontraction with the prostaglandin analogue U46619, concentration-response experiments were performed with acetazolamide and dorzolamide before and after removal of the perivascular retina. The experiments were performed at normal pH and during acidosis, during normocapnia and hypercapnia, as well as in the nominal absence of CO(2) and HCO(3)(-).
  
  
  RESULTS
  The maximum relaxation was significantly lower and the EC(50) significantly higher during normal pH compared with acidosis (P = 0.002 and P < 0.0001, respectively), but neither the maximum relaxation nor EC(50) was changed by hypercapnia (P = 0.054 and P = 0.57, respectively). The findings confirmed that carbonic anhydrase-induced vasodilation depends on the perivascular retinal tissue and that dorzolamide produces significantly more pronounced relaxation than does acetazolamide. EC(50) of carbonic anhydrase inhibitor-induced vasorelaxation and the maximum relaxation of dorzolamide were unchanged in the nominal absence of CO(2) and HCO(3)(-) (P = 0.65 and P < 0.0001, respectively).
  
  
  CONCLUSIONS
  The vasodilating effect of carbonic anhydrase inhibitors on porcine retinal arterioles depends on the perivascular retinal tissue and acidosis, but not on hypercapnia. The effect involves mechanisms other than carbonic anhydrase inhibition.
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Maria Skytte
authors.initials: MS
authors.lastname: Torring
authors.forename: Kim
authors.initials: K
authors.lastname: Holmgaard
authors.forename: Anders
authors.initials: A
authors.lastname: Hessellund
authors.forename: Christian
authors.initials: C
authors.lastname: Aalkjaer
authors.forename: Toke
authors.initials: T
authors.lastname: Bek