Sensory nitrergic meningeal vasodilatation and non-nitrergic plasma extravasation in anaesthesized rats.
The aim of the present study was to evaluate the role of nitric oxide (NO) of sensory neural origin in neurogenic inflammatory response in the trigeminovascular system. Antidromic vasodilatation and plasma extravasation in response to electrical stimulation (15 V, 5 Hz, 0.5 ms, 100 impulses) of the trigeminal ganglion were investigated in the dura mater and nasal mucosa/upper eyelid by laser Doppler flowmetry and [(125)I]-labelled bovine serum albumin, respectively. Electrical stimulation of the trigeminal ganglion of rats elicited a reproducible ipsilateral enhancement of both meningeal and nasal mucosal blood flow. N(omega)-nitro-L-arginine (L-NNA; 4, 8, and 16 mg/kg, i.v.), a nonselective inhibitor of nitric oxide synthase (NOS), inhibited antidromic vasodilatation both in the dura mater (15.86+/-2.05%, 22.82+/-2.51%, and 36.28+/-4.37%) and nasal mucosa (35.46+/-8.57%, 58.72+/-9.2%, and 89.99+/-8.94%) in a dose-dependent manner. Specific inhibitors of neuronal NOS, 7-nitroindazole (7-NI; 20 mg/kg, i.v.) and 3-bromo-7-nitroindazole (3Br-7NI; 10 mg/kg, i.v.) were administered to assess the possible role of NO released from the trigeminal sensory fibres. The meningeal vasodilatation was inhibited by both 3Br-7NI and 7-NI (63.36+/-7.7% and 49+/-6.5%, respectively). The nasal hyperaemic response was also reduced by 3Br-7NI (78.26+/-8.7%). Plasma extravasation in the dura mater and upper eyelid evoked by electrical stimulation of the trigeminal ganglion (25 V, 5 Hz, 0,5 ms, 5 min), expressed as extravasation ratios (ERs) of the stimulated vs. nonstimulated sides, was 1.80+/-0.8 and 4.63+/-1.24, respectively. This neurogenic oedema formation was not inhibited by neither L-NNA nor 3Br-7NI. It is concluded that neural nitrergic mechanisms are involved in the meningeal vasodilatation evoked by electrical stimulation of the trigeminal ganglion.
Peitl
Barna
B
Department of Pharmacology and Pharmacotherapy, University of Debrecen, Nagyerdei krt. 98, Debrecen H-4032, Hungary. barna.peitl@king.pharmacol.dote.hu
Németh
József
J
Szolcsányi
János
J
Szilvássy
Zoltán
Z
Pórszász
Róbert
R
D000818:Animals; D002199:Capillary Permeability; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000502:physiology; D008578:Meninges / Q000098:blood supply*; D009297:Nasal Mucosa / Q000098:blood supply / Q000187:drug effects; D026602:Nitrergic Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012668:Trigeminal Ganglion / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
C106731:3-bromo-7-nitroindazole; D004791:Enzyme Inhibitors; D007191:Indazoles; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole