Nitric oxide: a modulator, but not a mediator, of neurovascular coupling in rat samatosensory cortex

We investigated the role of nitric oxide (NO)/cGMP in the coupling of neuro nal activation to regional cerebral blood flow (rCBF) in alpha-chloralose-a nesthetized rats. Whisker deflection (60 s) increased rCBF by 18 +/- 3%. NO synthase (NOS) inhibition by N-omega-nitro-L-arginine (L-NNA; topically) r educed the rCBF response to 9 +/- 4% and resting rCBF to 80 +/- 8%. NO dono rs [S-nitroso-N-acetylpenicillamine (SNAP; 50 mu M), 3-morpholinosydnonimin e (10 mu M)] or 8-bromoguanosine 3',5'-cyclic-monophosphate (8-BrcGMP; 100 mu M)] restored resting rCBF and L-NNA-induced attenuation of the whisker r esponse in the presence of L-NNA, whereas the NO-independent vasodilator pa paverine (1 mM) had no effect on the whisker response. Basal cGMP levels we re decreased to 35% by L-NNA and restored to 65% of control by subsequent S NAP 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]quinoxali n-1-one (ODQ; 100 mu M) 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 som atosensory cortex and that this effect is mainly mediated by cGMP. L-NNA-in duced vasomotion was significantly reduced during increased neuronal activi ty and after restoration of basal NO levels, but not after restoration of c GMP.