Increase in meningeal blood flow by nitric oxide--interaction with calcitonin gene-related peptide receptor and prostaglandin synthesis inhibition.
This study addresses possible interactions of the vasodilators nitric oxide (NO), calcitonin gene-related peptide (CGRP) and prostaglandins, which may be implicated in the generation of vascular headaches. Local application of the NO donator diethylamine-NONOate (NONOate) to the exposed dura mater encephali of the rat caused dose-dependent increases in meningeal blood flow recorded by laser Doppler flowmetry. Pre-application of the CGRP receptor antagonist CGRP8-37 significantly attenuated the evoked blood flow increases, while the cyclooxygenase inhibitors acetylsalicylic acid and metamizol were only marginally effective. Stimulation of rat dura mater with NONOate in vitro caused increases in CGRP release. NADPH-diaphorase activity indicating NO production was restricted to the endothelium of dural arterial vessels. We conclude that increases in meningeal blood flow caused by NO depend partly on the release and vasodilatory action of CGRP from dural afferents, while prostaglandins are not significantly involved.
Strecker
T
T
Department of Physiology and Experimental Pathophysiology, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany, Hungary.
Dux
M
M
Messlinger
K
K
D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater / Q000201:enzymology; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D008578:Meninges / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000502:physiology
D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D018015:Receptors, Calcitonin Gene-Related Peptide; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D009252:NADPH Dehydrogenase; D015232:Dinoprostone