CALCITONIN-GENE-RELATED PEPTIDE PROMOTES CEREBROVASCULAR DILATION DURING CORTICAL SPREADING DEPRESSION IN RABBITS

We examined the role of calcitonin gene-related peptide (CGRP) in cort ical spreading depression (CSD)-induced dilation of rabbit pial arteri oles. In urethan-anesthetized rabbits instrumented with a closed crani al window, CSD induction with KCl dilated pial arterioles from 86 +/- 10 to 132 +/- 13 (means +/- SE, n = 6) mu m (a 54 +/- 9% increase). To pical administration of 12.8 mu M CGRP-(8-37), a competitive inhibitor of the CGRP receptor, reduced CSD-induced pial dilation from 54 +/- 9 % baseline to 33 +/- 9% (P < 0.05). Removal of the receptor antagonist from the brain surface restored CSD-induced dilation to 59 +/- 11% (P < 0.05, compared with the response with the antagonist present). In o ther animals, we showed that this dose of the CGRP antagonist attenuat ed arteriolar dilation to topically applied 10(-7) M CGRP (n = 5), but it did not alter arteriolar dilation to arterial hypercapnia. We also evaluated the dilator potency of substance P (SP) compared with CGRP. Dilation with 10(-7) M SP was only 22 +/- 11%, whereas arterioles dil ated to 57 +/- 7% above baseline diameter with 10(-7) M CGRP. We concl ude that CGRP contributes to the transient arteriolar dilation that is characteristic of CSD.