Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow

Strecker, Thomas; Dux, Mária; Meßlinger, Karl

doi:10.1159/000067206

Cited by 87 publications

(77 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…NO donors, though at much higher doses than used in the present study, released CGRP from the rat cranial dura, promoting increases in meningeal blood flow (20). In a rat model of intravital microscopy, neurogenic vasodilatation of meningeal blood vessels was attenuated by inhibition of nNOS, while CGRP-induced vasodilatation was attenuated by eNOS inhibition (65).…”

Section: Implications For Vascular Versus Neuronal Hypotheses Of Migrmentioning

confidence: 51%

Increase in CGRP- and nNOS-immunoreactive neurons in the rat trigeminal ganglion after infusion of an NO donor

et al. 2010

Self Cite

View full text Add to dashboard Cite

Background: Nitrovasodilators, such as glyceroltrinitrate (GTN), which produce nitric oxide (NO) in the organism, are known to cause delayed headaches in migraineurs, accompanied by increased plasma levels of calcitonin gene-related peptide (CGRP) in the cranial venous outflow. Increases in plasma CGRP and NO metabolites have also been found in spontaneous migraine attacks. In a rat model of meningeal nociception, infusion of NO donors induced activity of neurons in the spinal trigeminal nucleus. Methods: Isoflurane-anaesthetised rats were intravenously infused with GTN (250 mg/kg) or saline for two hours and fixed by perfusion after a further four hours. Cryosections of dissected trigeminal ganglia were immunostained for detection of CGRP and neuronal NO synthase (nNOS). The ganglion neurons showing immunofluorescence for either of these proteins were counted. Results: The proportions of CGRP-and nNOS-as well as double-immunopositive neurons were increased after GTN infusion compared to saline treatment in all parts of the trigeminal ganglion (CGRP) or restricted to the ophthalmic region (nNOS). The size of immunopositive neurons was not significantly different compared to controls. Conclusion: High levels of NO may induce the expression or availability of CGRP and nNOS. Similar changes may be involved in nitrovasodilator-induced and spontaneous headache attacks in migraineurs.

show abstract

Section: Implications For Vascular Versus Neuronal Hypotheses Of Migrmentioning

confidence: 51%

Increase in CGRP- and nNOS-immunoreactive neurons in the rat trigeminal ganglion after infusion of an NO donor

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…(2008) recently have reported NO derived from endothelial NOS maintains the threshold for initiating CSD in rodent and human brains. Additionally, NO produced by the cortex or cerebral vasculature may affect CGRP release in the dura mater (Strecker et al ., 2002) and thus modulate the degree of pain associated with migraines.…”

Section: Mechanisms Of Cerebral Hyperemia During Csdmentioning

confidence: 99%

Mechanisms involved in the cerebrovascular dilator effects of cortical spreading depression

Busija¹,

Bari²,

Domoki³

et al. 2008

Progress in Neurobiology

View full text Add to dashboard Cite

Cortical spreading depression (CSD) leads to dramatic changes in cerebral hemodynamics. However, mechanisms involved in promoting and counteracting cerebral vasodilator responses are unclear.Here we review the development and current status of this important field of research especially with respect to the role of perivascular nerves and nitric oxide (NO). It appears that neurotransmitters released from the sensory and the parasympathetic nerves associated with cerebral arteries, and NO released from perivascular nerves and/or parenchyma, promote cerebral hyperemia during CSD. However, the relative contributions of each of these factors vary according to species studied. Related to CSD, axonal and reflex responses involving trigeminal afferents on the pial surface lead to increased blood flow and inflammation of the overlying dura mater. Counteracting the cerebral vascular dilation is the production and release of constrictor prostaglandins, at least in some species, and other possibly yet unknown agents from the vascular wall. The cerebral blood flow response in healthy human cortex has not been determined, and thus it is unclear whether the cerebral oligemia associated with migraines represents the normal physiological response to a CSD-like event or represents a pathological response. In addition to promoting cerebral hyperemia, NO produced during CSD appears to initiate signaling events which lead to protection of the brain against subsequent ischemic insults. In summary, the cerebrovascular response to CSD involves multiple dilator and constrictor factors produced and released by diverse cells within the neurovascular unit, with the contribution of each of these factors varying according to the species examined.

show abstract

“…Another 10 hemisected skulls were treated with NONOate (10 -4 M), a NO donator, which has previously been shown to release CGRP from the dura (25). The basal level of immunoreactive histamine was 13.9 Ϯ 0.7 pg/ml and after application of NONOate the value was 13.3 Ϯ 1.4 pg/ml, i.e.…”

Section: Release Of Histaminementioning

confidence: 99%

Interaction of Calcitonin Gene-Related Peptide, Nitric Oxide and Histamine Release in Neurogenic Blood Flow and Afferent Activation in The Rat Cranial Dura Mater

et al. 2007

View full text Add to dashboard Cite

Calcitonin gene-related peptide (CGRP), nitric oxide (NO) and histamine are implicated in primary headaches but their role in vascular and nociceptive events in the dura mater is not well described. In an in vitro preparation of the hemisected rat skull, CGRP and histamine release from the cranial dura was measured using enzyme-linked immunoassays. While the NO donator NONO(ate) (10(-4) M) was without effect, CGRP (10(-5) M) induced considerable histamine release from the rat cranial dura, which was blocked by the CGRP receptor antagonist CGRP(8-37) (10(-5) M). Conversely, histamine (10(-4) M) did not stimulate CGRP release. In vitro recordings from single rat meningeal afferents showed that only one of 12 mechanically identified units but several mechanically insensitive units responded to histamine (up to 10(-5) M). Increases in meningeal blood flow after histamine application (10(-4) M) to the rat cranial dura remained unchanged during CGRP receptor blockade with CGRP(8-37), inhibition of NO synthesis with L-NAME (20 mg/kg i.v.) and H(3) receptor blockade with thioperamide (10(-4) M). We conclude that histamine produces direct vasodilatation and activates a subset of largely non-mechanically sensitive, non-CGRP containing afferents in the rat meninges. Histamine is released from meningeal mast cells which are stimulated by CGRP. Similar mechanisms may be involved in the pathogenesis of headaches.

show abstract

Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow

Cited by 87 publications

References 45 publications

Increase in CGRP- and nNOS-immunoreactive neurons in the rat trigeminal ganglion after infusion of an NO donor

Increase in CGRP- and nNOS-immunoreactive neurons in the rat trigeminal ganglion after infusion of an NO donor

Mechanisms involved in the cerebrovascular dilator effects of cortical spreading depression

Interaction of Calcitonin Gene-Related Peptide, Nitric Oxide and Histamine Release in Neurogenic Blood Flow and Afferent Activation in The Rat Cranial Dura Mater

Contact Info

Product

Resources

About