EFFECTS OF SUBARACHNOID HEMORRHAGE ON VASCULAR-RESPONSES TO CALCITONIN-GENE-RELATED PEPTIDE AND ITS RELATED 2ND-MESSENGERS

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and a p rimary signaling molecule in neurovascular communication. In the prese nt study, the authors examined cerebrovascular responses to CGRP and i ts related second messenger systems during cerebral vasospasm induced by subarachnoid hemorrhage (SAH). Tension measurements were performed in vitro on ring strips of basilar arteries obtained from rabbits subj ected to artificial SAH and from control (non-SAH) animals. in vessels from SAH animals, which were preconstricted with serotonin, the vasor elaxant response to CGRP was attenuated. Because it has been suggested that vasodilation elicited by CGRP is mediated by cyclic 3',5'-adenos ine monophosphate (cAMP) and/or cyclic 3',5'-guanosine monophosphate ( cGMP), the vascular effects of directly activating these second messen ger systems were also examined. The relaxant effect of forskolin, whic h activates adenylate cyclase directly, was slightly enhanced after SA H. In contrast, the relaxant effect of nitroglycerin (GTN), which acti vates soluble guanylate cyclase directly, was unchanged after SAH. The attenuation of CGRP-induced vasorelaxation could be the result of a m odification in its ability to stimulate the production of second messe ngers. Experiments testing the capacity of CGRP to elevate cAMP levels showed no significant differences between vessels from non-SAH and SA H animals. Similarly, the resting levels of cAMP and the forskolin ind uced elevations of cAMP did not differ between non-SAH and SAH animals . In contrast, cGMP levels were lower in resting and CGRP-treated vess els from SAH animals than in those from non-SAH animals. No significan t differences in the levels of cGMP were observed between non-SAH and SAH vessels treated with GTN. This study indicates that CGRP-induced v asodilation is attenuated during vasospasm in a rabbit model of SAH. T he findings also demonstrate that vasodilatory responses mediated by c AMP and cGMP are intact, although the levels of cGMP in SAH vessels ar e reduced. Together, these observations suggest that an attenuation in the capacity of vessels to dilate in response to CGRP occurs during c erebral vasospasm, and this change in CGRP vasoactivity is a result of modifications prior to, or independent of, the elevation of cyclic nu cleotide second messengers.