Comparison of responses to vasoactive drugs in human and rat cerebral arteries using myography and pressurized cerebral artery method

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 pECE(50) for SNP, aCGRP, PACAP-27 and PACAP-38 were not significant between the species. PGE(2) had no noticeable effect on human arteries in vitro. Conclusion: 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.