title: Comparison of responses to vasoactive drugs in human and rat cerebral arteries using myography and pressurized cerebral artery method.
abstract: BACKGROUND
  Dilatation of cranial vessels has been proposed as a part of the cascade that initiates an episode of migraine. This is based on the observation that intravenous administration of several substances with vasodilator properties can trigger migraine-like symptoms in migraineurs.
  
  
  METHODS
  We used in vitro myography of human cerebral arteries and in vitro pressurized arteriography of rat middle cerebral artery (MCA) to evaluate the vasomotor responses of cerebral arteries to increasing concentrations of vasoactive substances used to elicit migraine-like attacks.
  
  
  RESULTS
  All substances except carbachol induced a strong vasodilatory response when applied to the abluminal side of a rat MCA but negligible response when applied to the luminal side. Luminal carbachol gave a strong dilatory response but a weak response at the abluminal side. The prostaglandins PGE(2) and epoprostenol constricted the rat MCA while human cerebral arteries relaxed. The pEC(50) of carbachol, histamine, epoprostenol, VIP and sildenafil differed significantly between cerebral arteries from man and rat. The differences in pEC(50) for SNP, αCGRP, PACAP-27 and PACAP-38 were not significant between the species. PGE(2) had no noticeable effect on human arteries in vitro.
  
  
  CONCLUSIONS
  All tested substances with the exception of VIP and carbachol have been found to elicit migraine-like attacks in migraineurs. Since these two agents have vasodilatory effects in humans, it suggests that vasodilatation is not the only reason for eliciting a migraine-like attack in migraineurs. In addition, there are significant species differences that show the importance of performing experiments in human vessels.
authors.affiliation: Division of Experimental Vascular Research, Institute of Clinical Science, Lund University, Sweden.
authors.forename: Gustaf
authors.initials: G
authors.lastname: Grände
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Nilsson
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000502:physiology*; D009213:Myography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents