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

Thomas Strecker, M. Dux, Karl Messlinger

Research output: Contribution to journalArticle

67 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 - 2002

Fingerprint

Dura Mater
Calcitonin Gene-Related Peptide
Nitric Oxide
Vascular Headaches
Nitric Oxide Donors
Calcitonin Gene-Related Peptide Receptors
S-Nitroso-N-Acetylpenicillamine
Extracellular Fluid
Immunoenzyme Techniques
Skull
Lasers
Animal Models
Gases

Keywords

  • Arterial blood flow
  • Calcitonin-gene-related peptide
  • Dura mater encephali
  • Migraine
  • Neuropeptides
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology

Cite this

Nitric oxide releases calcitonin-gene-related peptide from rat dura mater encephali promoting increases in meningeal blood flow. / Strecker, Thomas; Dux, M.; Messlinger, Karl.

In: Journal of Vascular Research, Vol. 39, No. 6, 2002, p. 489-496.

Research output: Contribution to journalArticle

@article{04b7d6001a8041629ff1e9a65c27cfcb,
title = "Nitric oxide releases calcitonin-gene-related peptide from rat dura mater encephali promoting increases in meningeal blood flow",
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.",
keywords = "Arterial blood flow, Calcitonin-gene-related peptide, Dura mater encephali, Migraine, Neuropeptides, Nitric oxide",
author = "Thomas Strecker and M. Dux and Karl Messlinger",
year = "2002",
doi = "10.1159/000067206",
language = "English",
volume = "39",
pages = "489--496",
journal = "Journal of Vascular Research",
issn = "1018-1172",
publisher = "S. Karger AG",
number = "6",

}

TY - JOUR

T1 - Nitric oxide releases calcitonin-gene-related peptide from rat dura mater encephali promoting increases in meningeal blood flow

AU - Strecker, Thomas

AU - Dux, M.

AU - Messlinger, Karl

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Arterial blood flow

KW - Calcitonin-gene-related peptide

KW - Dura mater encephali

KW - Migraine

KW - Neuropeptides

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=0036957637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036957637&partnerID=8YFLogxK

U2 - 10.1159/000067206

DO - 10.1159/000067206

M3 - Article

C2 - 12566974

AN - SCOPUS:0036957637

VL - 39

SP - 489

EP - 496

JO - Journal of Vascular Research

JF - Journal of Vascular Research

SN - 1018-1172

IS - 6

ER -