title: Pial arteriolar constriction to alpha 2-adrenergic agonist dexmedetomidine in the rat.
abstract: Dexmedetomidine (Dex) is an alpha 2-adrenergic agonist that decreases cerebral blood flow (CBF) when administered systemically. It is unclear whether cerebral vasoconstriction is mediated by a local effect on cerebral vessels or by a remote neural mechanism. In the present study, we compared the pial arteriole responses to locally and systemically administered Dex with and without local application of the specific alpha 2-adrenergic antagonist atipamezole. Six groups of male rats (n = 7 each) were anesthetized with isoflurane and prepared for measurements of small (20-39 microns), medium (40-59 microns), and large (60-79 microns) pial arteriole diameter by intravital microscopy or for regional CBF measurement by the radiolabeled-microsphere method. Local application of Dex caused dose-dependent constriction that was significant starting at 10(-8) M for small and medium-sized arterioles and at 10(-7) M for large arterioles. Constriction to 10(-5) M in small [21 +/- 2% (SE)], medium (21 +/- 2%), and large (15 +/- 1%) arterioles was almost completely blocked by local application of 10(-4) M atipamezole. Intravenous administration of Dex at 1 microgram/kg decreased CBF and caused modest arteriolar constriction that began to resolve 8 min after administration. A dose of 10 micrograms/kg constricted arterioles of all sizes with constriction beginning to resolve after approximately 10 min. Local application of atipamezole (10(-4) M) slightly blunted the response to 1 micrograms/kg of intravenous Dex but did not substantially limit constriction after 10 micrograms/kg. These data demonstrate that pial arterioles are capable of substantial constriction to Dex by a local alpha 2-adrenergic mechanism. However, the inability of locally applied atipamezole to substantially inhibit the vasoconstrictor response to systemically administered Dex suggests that Dex might also cause vasoconstriction indirectly through actions at other sites in the central nervous system.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4961, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Asano
authors.forename: R C
authors.initials: RC
authors.lastname: Koehler
authors.forename: T
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: R W
authors.initials: RW
authors.lastname: McPherson
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D020926:Medetomidine; D010477:Perfusion; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D020926:Medetomidine