ARTERIOLAR CONSTRICTION TO ALPHA(2)-ADRENERGIC AGONIST DEXMEDETOMIDINE IN THE RAT

Dexmedetomidine (Dex) is an alpha(2)-adrenergic agonist that decreases cerebral blood flow (CBF) when administered systemically. It is uncle ar 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 a lpha(2)-adrenergic antagonist atipamezole. Six groups of male rats (n = 7 each) were anesthetized with isoflurane and prepared for measureme nts of small (20-39 mu m), medium (40-59 Fern), and large (60-79 mu m) 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 startin g at 10(-8) M for small and medium-sized arterioles and at 10(-7) M fo r large arterioles. Constriction to 10(-5) M in small [21 +/- 2% (SE)] , medium (21 +/- 2%), and large (15 +/- 1%) arterioles was almost comp letely blocked by local application of 10(-4) M atipamezole. Intraveno us administration of Dex at 1 mu g/kg decreased CBF and caused modest arteriolar constriction that began to resolve 8 min after administrati on. A dose of 10 mu g/kg constricted arterioles of all sizes with cons triction beginning to resolve after similar to 10 min. Local applicati on of atipamezole (10(-4) M) slightly blunted the response to 1 mu g/k g of intravenous Dex but did not substantially limit constriction afte r 10 mu g/kg. These data demonstrate that pial arterioles are capable of substantial constriction to Dex by a local alpha(2)-adrenergic mech anism. However, the inability of locally applied atipamezole to substa ntially inhibit the vasoconstrictor response to systemically administe red Dex suggests that Lex might also cause vasoconstriction indirectly through actions at other sites in the central nervous system.