Nitric oxide releases calcitonin-gene-related peptide from rat dura mater encephali promoting increases in meningeal blood flow

Thomas Strecker, Mária Dux, Karl Messlinger

Research output: Article

69 Citations (Scopus)

Abstract

Nitric oxide (NO) and calcitonin-gene-related peptide (CGRP) are implicated in the pathophysiology of vascular headaches. We studied the interaction of these two vasodilatory mediators in an animal model and suggest that NO may increase meningeal blood flow not only by its direct vasodilatory action but also by stimulating CGRP release. First, CGRP release from the rat cranial dura mater was measured in vitro using an enzyme immunoassay. Hemisected skulls with adhering dura mater were filled with synthetic interstitial fluid and stimulated with the NO donor diethylamine-NONOate (10-5-10-3 M) or with NO gas (1,000 ppm), which caused concentration-dependent increases in CGRP release up to 166.8%. Second, meningeal blood flow was recorded in vivo in the exposed dura mater using laser Doppler flow-metry. Topical application of the NO donors NONOate, S-nitroso-N-acetylpenicillamine and N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethenamine (10-5-10-3M) caused concentration-dependent increases in blood flow. These increases were significantly reduced by local preliminary application of the CGRP receptor antagonist CGRP8-37 (10-4 M). We conclude that NO stimulates the) release of CGRP from dural afferents. The blood-flow-increasing effect of NO seems to be partly mediated by CGRP. The interaction of NO and CGRP may be relevant for the development of vascular headaches.

Original languageEnglish
Pages (from-to)489-496
Number of pages8
JournalJournal of Vascular Research
Volume39
Issue number6
DOIs
Publication statusPublished - dec. 1 2002

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Nitric oxide releases calcitonin-gene-related peptide from rat dura mater encephali promoting increases in meningeal blood flow'. Together they form a unique fingerprint.

  • Cite this