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Meningeal blood flow is controlled by H2 S-NO crosstalk activating a HNO-TRPA1-CGRP signalling pathway.

ABSTRACT: BACKGROUND AND PURPOSE:Meningeal blood flow is controlled by CGRP released from trigeminal afferents and NO mainly produced in arterial endothelium. The vasodilator effect of NO may be due to the NO-derived compound, nitroxyl (HNO), generated through reaction with endogenous H2 S. We investigated the involvement of HNO in CGRP release and meningeal blood flow. EXPERIMENTAL APPROACH:Blood flow in exposed dura mater of rats was recorded by laser Doppler flowmetry. CGRP release from the dura mater in the hemisected rat head was quantified using an elisa. NO and H2 S were localized histochemically with specific sensors. KEY RESULTS:Topical administration of the NO donor diethylamine-NONOate increased meningeal blood flow by 30%. Pretreatment with oxamic acid, an inhibitor of H2 S synthesis, reduced this effect. Administration of Na2 S increased blood flow by 20%, an effect abolished by the CGRP receptor antagonist CGRP8-37 or the TRPA1 channel antagonist HC030031 and reduced when endogenous NO synthesis was blocked. Na2 S dose-dependently increased CGRP release two- to threefold. Co-administration of diethylamine-NONOate facilitated CGRP release, while inhibition of endogenous NO or H2 S synthesis lowered basal CGRP release. NO and H2 S were mainly localized in arterial vessels, HNO additionally in nerve fibre bundles. HNO staining was lost after treatment with L-NMMA and oxamic acid. CONCLUSIONS AND IMPLICATIONS:NO and H2 S cooperatively increased meningeal blood flow by forming HNO, which activated TRPA1 cation channels in trigeminal fibres, inducing CGRP release. This HNO-TRPA1-CGRP signalling pathway may be relevant to the pathophysiology of headaches.

SUBMITTER: Dux M

PROVIDER: S-EPMC4728414 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Meningeal blood flow is controlled by H2 S-NO crosstalk activating a HNO-TRPA1-CGRP signalling pathway.

Dux Mária M Will Christine C Vogler Birgit B Filipovic Milos R MR Messlinger Karl K

British journal of pharmacology 20150612 3

<h4>Background and purpose</h4>Meningeal blood flow is controlled by CGRP released from trigeminal afferents and NO mainly produced in arterial endothelium. The vasodilator effect of NO may be due to the NO-derived compound, nitroxyl (HNO), generated through reaction with endogenous H2 S. We investigated the involvement of HNO in CGRP release and meningeal blood flow.<h4>Experimental approach</h4>Blood flow in exposed dura mater of rats was recorded by laser Doppler flowmetry. CGRP release from ...[more]

PMID: 25884403

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Project description:PurposeTo compare quantitative values of cerebral blood flow (CBF) derived from dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging with reference standard positron emission tomography (PET) in patients with confirmed cerebrovascular occlusive disease.Materials and methodsLocal institutional review board approval and informed consent were obtained for a prospective study of 18 patients (six men, 12 women; age range, 28-71 years; mean age, 45 years ± 10.4 [standard deviation]) with angiographically confirmed Moyamoya (n = 8) or internal carotid artery occlusions (n = 10). DSC MR images and oxygen 15-labeled water (H(2)[(15)O]) PET images were acquired on the same day. DSC images were postprocessed to yield parametric images of CBF (in mL/100 g/min), coregistered, and analyzed using grid-based regions of interest. Mean values of CBF in each region of interest from MR imaging and PET data sets were compared. Correlations for each patient were determined and overall agreement between pooled MR imaging and PET CBF was reported using linear regression analysis and Bland-Altman plots.ResultsStrong correlations (r(2) ? 0.55) were found between MR imaging and PET CBF values in all patients. Use of the bookend approach was found to underestimate CBF predictably across the patient cohort (mean slope, 0.82; standard deviation, 0.18; slope of aggregated data, 0.75). This allowed for a simple rescaling of MR imaging values producing strong agreement with PET values in the aggregated data (r(2) = 0.66; slope = 1.00; intercept = 0.00).ConclusionThe data show that the bookend MR imaging technique produces similar results for quantitative CBF between DSC MR imaging and H(2)[(15)O] PET. Although MR-derived CBF underestimated PET-derived CBF, the patient-to-patient variability in the slopes of the linear MR and PET relationships was significantly smaller than a competing quantitation technique. As a result, the bookend technique appears to more predictably measure quantitative CBF in a clinical setting.

Dataset Information

Meningeal blood flow is controlled by H2 S-NO crosstalk activating a HNO-TRPA1-CGRP signalling pathway.

Publications

Meningeal blood flow is controlled by H2 S-NO crosstalk activating a HNO-TRPA1-CGRP signalling pathway.

Similar Datasets

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