title: A novel approach to the study of human microcirculation: Reactivity to locally applied angiotensin II in the conjunctival microvascular bed.
abstract: OBJECTIVE
  To develop a state-of-the-art, computer-assisted intravital microscopy protocol to evaluate directly the effects of topically applied drugs on conjunctival arteriolar and venular diameters.
  
  
  METHODS
  Fifty-one normotensive volunteers were studied. Video-recordings of the bulbar conjunctival microcirculation were made before and following eye drops containing angiotensin II (AngII) (0.001% w/w, or 0.01%) or phenylephrine (0.25%). The computer-assisted analyses of arteriolar and venular diameters were performed off-line. In different protocols the microvascular reactivity to the different eye drops were compared.
  
  
  RESULTS
  AngII (0.01%) eye drops, but not AngII (0.001%), induced significant constriction in both arterioles (median, 19%) and venules (13%). Phenylephrine eye drops (pharmacological control) induced similar arteriolar (18%) and venular (12%) constrictions. Repeated AngII challenges with a 30-min interval revealed reproducible vasoconstriction responses (median arteriolar constriction, 11 and 17%, respectively; NS). The vasoconstriction responses following AngII challenges on two consecutive days revealed reproducible responses (median arteriolar constriction, 13 and 11%, respectively; NS).
  
  
  CONCLUSIONS
  The present results demonstrate that the proposed model for noninvasive intravital video-microscopy of the conjunctival microcirculation is sensitive for measuring direct arteriolar and venular reactivity following topically applied drugs. We consider this model a valuable tool for sophisticated research on in-vivo microvascular reactivity in humans.
authors.affiliation: Department of Internal Medicine, University Hospital Maastricht and Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands. B.Houben@intmed.unimaas.nl
authors.forename: Alphons J H M
authors.initials: AJ
authors.lastname: Houben
authors.forename: J Philip
authors.initials: JP
authors.lastname: Burgwinkel
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects; D003228:Conjunctiva / Q000098:blood supply* / Q000187:drug effects*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D018715:Microscopy, Video / Q000379:methods*; D010656:Phenylephrine / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014699:Venules / Q000187:drug effects
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine