Calcitonin gene-related peptide promotes cerebrovascular dilation during cortical spreading depression in rabbits

We examined the role of calcitonin gene-related peptide (CGRP) in cortical spreading depression (CSD)-induced dilation of rabbit pial arterioles. In urethan-anesthetized rabbits instrumented with a closed cranial window, CSD induction with KCl dilated pial arterioles from 86 +/- 10 to 132 +/- 13 (mean +/- SE, n = 6) microns (a 54 +/- 9% increase). Topical administration of 12.8 microM 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 other animals, we showed that this dose of the CGRP antagonist attenuated 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 dilated to 57 +/- 7% above baseline diameter with 10(-7) M CGRP. We conclude that CGRP contributes to the transient arteriolar dilation that is characteristic of CSD.