Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital

Vascular pathology of large cerebral arteries in experimental subarachnoid hemorrhage: Vasoconstriction, functional CGRP depletion and maintained CGRP sensitivity

Research output: Contribution to journalJournal articleResearchpeer-review

  1. CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Gasotransmitters and the immune system: Mode of action and novel therapeutic targets

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Identifying New Antimigraine Targets: Lessons from Molecular Biology

    Research output: Contribution to journalReviewpeer-review

  2. Oral rimegepant for migraine prevention

    Research output: Contribution to journalComment/debateResearchpeer-review

View graph of relations

Subarachnoid hemorrhage (SAH) is associated with increased cerebral artery sensitivity to vasoconstrictors and release of the perivascular sensory vasodilator CGRP. In the current study the constrictive phenotype and the vasodilatory effects of exogenous and endogenous perivascular CGRP were characterized in detail applying myograph technology to cerebral artery segments isolated from experimental SAH and sham-operated rats. Following experimental SAH, cerebral arteries exhibited increased vasoconstriction to endothelin-1, 5-hydroxytryptamine and U46419. In addition, depolarization-induced vasoconstriction (60mM potassium) was significantly increased, supporting a general SAH-associated vasoconstrictive phenotype. Using exogenous CGRP, we demonstrated that sensitivity of the arteries to CGRP-induced vasodilation was unchanged after SAH. However, vasodilation in response to capsaicin (100nM), a sensory nerve activator used to release perivascular CGRP, was significantly reduced by SAH (P = 0.0079). Because CGRP-mediated dilation is an important counterbalance to increased arterial contractility, a reduction in CGRP release after SAH would exacerbate the vasospasms that occur after SAH. A similar finding was obtained with artery culture (24h), an in vitro model of SAH-induced vascular dysfunction. The arterial segments maintained sensitivity to exogenous CGRP but showed reduced capsaicin-induced vasodilation. To test whether a metabolically stable CGRP analogue could be used to supplement the loss of perivascular CGRP release in SAH, SAX was systemically administered in our in vivo SAH model. SAX treatment, however, induced CGRP-desensitization and did not prevent the development of vasoconstriction in cerebral arteries after SAH.

Original languageEnglish
JournalEuropean Journal of Pharmacology
Pages (from-to)109-118
Number of pages10
Publication statusPublished - 2019

Bibliographical note

Copyright © 2019 Elsevier B.V. All rights reserved.

    Research areas

  • Artery culture, Basilar artery, CGRP, CGRP analogue, CGRP receptor, Subarachnoid hemorrhage

ID: 56377850