title: Effects of subarachnoid hemorrhage on vascular responses to calcitonin gene-related peptide and its related second messengers.
abstract: Calcitonin gene-related peptide (CGRP) is a potent vasodilator and a primary signaling molecule in neurovascular communication. In the present study, the authors examined cerebrovascular responses to CGRP and its 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 subjected to artificial SAH and from control (non-SAH) animals. In vessels from SAH animals, which were preconstricted with serotonin, the vasorelaxant response to CGRP was attenuated. Because it has been suggested that vasodilation elicited by CGRP is mediated by cyclic 3',5'-adenosine monophosphate (cAMP) and/or cyclic 3',5'-guanosine monophosphate (cGMP), the vascular effects of directly activating these second messenger systems were also examined. The relaxant effect of forskolin, which activates adenylate cyclase directly, was slightly enhanced after SAH. In contrast, the relaxant effect of nitroglycerin (GTN), which activates soluble guanylate cyclase directly, was unchanged after SAH. The attenuation of CGRP-induced vasorelaxation could be the result of a modification in its ability to stimulate the production of second messengers. Experiments testing the capacity of CGRP to elevate cAMP levels showed no significant differences between vessels from non-SAH and SAH animals. Similarly, the resting levels of cAMP and the forskolin-induced elevations of cAMP did not differ between non-SAH and SAH animals. In contrast, cGMP levels were lower in resting and CGRP-treated vessels from SAH animals than in those from non-SAH animals. No significant differences in the levels of cGMP were observed between non-SAH and SAH vessels treated with GTN. This study indicates that CGRP-induced vasodilation is attenuated during vasospasm in a rabbit model of SAH. The findings also demonstrate that vasodilatory responses mediated by cAMP and cGMP are intact, although the levels of cGMP in SAH vessels are reduced. Together, these observations suggest that an attenuation in the capacity of vessels to dilate in response to CGRP occurs during cerebral vasospasm, and this change in CGRP vasoactivity is a result of modifications prior to, or independent of, the elevation of cyclic nucleotide second messengers.
authors.affiliation: Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville, USA.
authors.forename: B
authors.initials: B
authors.lastname: Sutter
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: A S
authors.initials: AS
authors.lastname: Arthur
authors.forename: N F
authors.initials: NF
authors.lastname: Kassell
authors.forename: K S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D005576:Colforsin / Q000032:analysis; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000503:physiopathology*; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D005576:Colforsin; D012701:Serotonin; D000242:Cyclic AMP; D005996:Nitroglycerin; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium