title: Opposite reactivity of meningeal versus cortical microvessels to the nitric oxide donor glyceryl trinitrate evaluated in vivo with two-photon imaging.
abstract: Vascular changes underlying headache in migraine patients induced by Glyceryl trinitrate (GTN) were previously studied with various imaging techniques. Despite the long history of medical and experimental use of GTN, its effects on the brain vasculature are still poorly understood presumably due to low spatial resolution of the imaging modalities used so far. We took advantage of the micrometer-scale vertical resolution of two-photon microscopy to differentiate between the vasodynamic effects of GTN on meningeal versus cortical vessels imaged simultaneously in anesthetized rats through either thinned skull or glass-sealed cranial window. Intermediate and small calibre vessels were visualized in vivo by imaging intravascular fluorescent dextran, and detection of blood flow direction allowed identification of individual arterioles and venules. We found that i.p.-injected GTN induced a transient constriction of meningeal arterioles, while their cortical counterparts were, in contrast, dilated. These opposing effects of GTN were restricted to arterioles, whereas the effects on venules were insignificant. Interestingly, the NO synthase inhibitor L-NAME did not affect the diameter of meningeal vessels but induced a constriction of cortical vessels. The different cellular environment in cortex versus meninges as well as distinct vessel wall anatomical features probably play crucial role in the observed phenomena. These findings highlight differential region- and vessel-type-specific effects of GTN on cranial vessels, and may implicate new vascular mechanisms of NO-mediated primary headaches.
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland ; Neurotar LTD, Helsinki, Finland.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Pryazhnikov
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kislin
authors.affiliation: Neurotar LTD, Helsinki, Finland.
authors.forename: Marina
authors.initials: M
authors.lastname: Tibeykina
authors.affiliation: Neurotar LTD, Helsinki, Finland.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Toptunov
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Ptukha
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Artem
authors.initials: A
authors.lastname: Shatillo
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Gröhn
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Rashid
authors.initials: R
authors.lastname: Giniatullin
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland ; Neurotar LTD, Helsinki, Finland.
authors.forename: Leonard
authors.initials: L
authors.lastname: Khiroug
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply; D008297:Male; D008578:Meninges / Q000098:blood supply; D055806:Microvessels / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020030:Nitric Oxide Donors; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester