title: Nitric oxide: a modulator, but not a mediator, of neurovascular coupling in rat somatosensory cortex.
abstract: We investigated the role of nitric oxide (NO)/cGMP in the coupling of neuronal activation to regional cerebral blood flow (rCBF) in alpha-chloralose-anesthetized rats. Whisker deflection (60 s) increased rCBF by 18 +/- 3%. NO synthase (NOS) inhibition by N(omega)-nitro-L-arginine (L-NNA; topically) reduced the rCBF response to 9 +/- 4% and resting rCBF to 80 +/- 8%. NO donors [S-nitroso-N-acetylpenicillamine (SNAP; 50 microM), 3-morpholinosydnonimine (10 microM)] or 8-bromoguanosine 3', 5'-cyclic-monophosphate (8-BrcGMP; 100 microM)] restored resting rCBF and L-NNA-induced attenuation of the whisker response in the presence of L-NNA, whereas the NO-independent vasodilator papaverine (1 mM) had no effect on the whisker response. Basal cGMP levels were decreased to 35% by L-NNA and restored to 65% of control by subsequent SNAP superfusion. Inhibition of neuronal NOS by 7-nitroindazole (7-NI; 40 mg/kg ip) or soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 100 microM) significantly reduced resting rCBF to 86 +/- 8 and 92 +/- 10% and whisker rCBF response to 7 +/- 4 and 12 +/- 3%, respectively. ODQ reduced tissue cGMP to 54%. 8-BrcGMP restored the whisker response in the presence of 7-NI or ODQ. We conclude that NO, produced by neuronal NOS, is a modulator in the coupling of neuronal activation and rCBF in rat somatosensory cortex and that this effect is mainly mediated by cGMP. L-NNA-induced vasomotion was significantly reduced during increased neuronal activity and after restoration of basal NO levels, but not after restoration of cGMP.
authors.affiliation: Department of Experimental Neurology, Humboldt University, Charité Hospital, 10098 Berlin, Germany. ut.lindauer@charite.de
authors.forename: U
authors.initials: U
authors.lastname: Lindauer
authors.forename: D
authors.initials: D
authors.lastname: Megow
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.forename: U
authors.initials: U
authors.lastname: Dirnagl
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D010208:Papaverine / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D014738:Vibrissae / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D010208:Papaverine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006162:Guanylate Cyclase; D006152:Cyclic GMP