Immunohistochemical localization of endothelial nitric oxide synthase in vessels of the dura mater of the Sprague-Dawley rat

Nemade, Rashmi V.; Lewis, Adam I.; Zuccarello, Mario; Keller, Jeffrey T.

doi:10.1016/0304-3940(95)11887-3

Cited by 14 publications

(7 citation statements)

References 11 publications

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“…Such constitutive endothelial expression suggests that prostanoids produced by COX-1 are likely involved in controlling the circulatory homeostasis of the dura, potentially in conjunction with endothelial NOS-derived nitric oxide [4, 14]. …”

Section: Discussionmentioning

confidence: 99%

Localization of COX-1 and COX-2 in the intracranial dura mater of the rat

Zhang

Kainz

Jakubowski

et al. 2009

Neuroscience Letters

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Primary headaches such as migraine can be aborted by systemic administration of non-steroidal antiinflammatory drugs (NSAIDs), potentially through the non-selective inhibition of cyclooxygenase (COX) activity in the intracranial meninges. In this study we have used single and double labeling immunohistochemistry to examine the distribution of the COX-1 and COX-2 isoforms in the intracranial dura mater of the rat and identify cell types that express them. COX-1 immunoreactivity was found in medium and small dural blood vessels and was co-expressed with the endothelial cell markers vimentin and the endothelial isoform of nitric oxide synthase (ecNOS). COX-1 was also found to be present in most dural mast cells. COX-2 was mainly expressed in ED2-positive resident dural macrophages. Constitutive COX-2 expression was also found in some axonal profiles, many of which were co-labeled with the nociceptor peptide marker CGRP. The findings suggest that NSAIDs may abort headache, at least in part, by inhibiting either neuronal or non-neuronal COX activity in the dura mater.

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Section: Discussionmentioning

confidence: 99%

Localization of COX-1 and COX-2 in the intracranial dura mater of the rat

Zhang

Kainz

Jakubowski

et al. 2009

Neuroscience Letters

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“…Relatively little information is available concerning the effects of NO in the extracerebral and extracranial circulation. eNOS has been localized in the vascular endothelium of the rat dura mater 19,20 and GTN is a strong vasodilator in this preparation. 21 Moreover, NO in guinea-pig dura mater induces extravasation and other changes similar to those induced by neurogenic inflammation.…”

Section: Effect Of No In the Cerebral And Extracerebral Circulationsmentioning

confidence: 91%

Nitric Oxide-Related Drug Targets in Headache

Olesen

2010

Neurotherapeutics

103

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Summary: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so-called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache. Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine.Similar evidence suggests an important role of NO in the tension-type headache and cluster headache.These very strong data from human experimentation make it highly likely that antagonizing NO effects will be effective in the treatment of primary headaches. Nonselective NOS inhibitors are likely to have side effects whereas selective compounds are now in early clinical trials. Antagonizing the rate limiting cofactor tetrahydrobiopterin seems another very likely new treatment. It is more unlikely that antagonism of cGMP or its formation will be feasible, but augmenting its breakdown via phosphodiesterase activation is a possibility, as well as other ways of inhibiting the NO-cGMP pathway.

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“…A prominent mast cell population immunoreactive for NOS has also been reported in the rat dura mater. 53 Using specific antibodies, eNOS has been found mainly in the middle meningeal artery, 54 whereas nNOS is present in thin nerve fiber ramifications running along branches of this artery (Fig. 1D).…”

Section: The Origins Of Cgrp and No In The Trigeminovascular Systemmentioning

confidence: 99%

CGRP and NO in the Trigeminal System: Mechanisms and Role in Headache Generation

et al. 2012

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Calcitonin gene-related peptide (CGRP) and metabolic products of nitric oxide (NO) are increased in jugular venous plasma during migraine attacks and other primary headaches. Patients suffering from primary headaches are particularly sensitive to CGRP and NO donors responding with delayed headaches to an infusion of either of these substances. Accordingly, both CGRP and NO are considered as key mediators in migraine, and clinical trials have shown that inhibitors of CGRP receptors and NO synthase are effective in treating migraine. There is an implicit understanding that CGRP and NO systems interact, and here, we review the body of preclinical work on these systems focusing on the trigeminovascular system in migraine. NO derives from various cell types via 3 isoforms of NO synthase, whereas CGRP is produced from a subset of trigeminal afferents. In rodents, NO donors cause activity alterations on different levels of the trigeminal system including enhancement of CGRP release, which in turn results in arterial vasodilatation and possibly mast cell degranulation in the meninges. The activity of spinal trigeminal neurons, which is a sensitive integrative measure for trigeminal activity, is partly under the control of CGRP and NO. Both mediators facilitate nociceptive transmission, possibly via presynaptic mechanisms. These functions are supported by immunolocalization of CGRP receptor components on 3 trigeminovascular levels: cranial dura mater, trigeminal ganglion, and spinal trigeminal nucleus. Current data support a relationship of CGRP and NO actions on all levels of the trigeminovascular system and emphasize central CGRP receptors as possible therapeutic targets.

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Immunohistochemical localization of endothelial nitric oxide synthase in vessels of the dura mater of the Sprague-Dawley rat

Cited by 14 publications

References 11 publications

Localization of COX-1 and COX-2 in the intracranial dura mater of the rat

Localization of COX-1 and COX-2 in the intracranial dura mater of the rat

Nitric Oxide-Related Drug Targets in Headache

CGRP and NO in the Trigeminal System: Mechanisms and Role in Headache Generation

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