Sustained attenuation of the cerebrovascular response to a 10 min whisker stimulation following neuronal nitric oxide synthase inhibition

We examined the effect of type I nitric oxide synthase (neuronal isoform of NOS, nNOS) inhibition on the temporal profile of the cortical blood flow (CoBF) changes induced by a relatively long period (10 min) of whisker stimulation. To address this issue, we used laser-Doppler flowmetry (LDF) to continuously monitor the CoBF in rats anesthetized with alpha-chloralose, in a control condition, and 30 and 60 min following 7-nitroindazole (25 mg/kg, i.p.). Mechanical stimulation of all whiskers for 10 min led to a continuous and sustained CoBF increase with a mean integral response of 4030+/-764%. After 30 and 60 min nNOS inhibition the CoBF response was significantly reduced by 52 and 68%, respectively (P<0. 05) with no evidence of any compensatory mechanism during the whole stimulation period. These data show that regulation of the cerebral blood flow in response to an increased neuronal activity is a dynamic and tonic process in which nNOS plays an essential role.

[1]  C. Iadecola,et al.  Regulation of the cerebral microcirculation during neural activity: is nitric oxide the missing link? , 1993, Trends in Neurosciences.

[2]  A. Villringer,et al.  Role of nitric oxide in the coupling of cerebral blood flow to neuronal activation in rats , 1993, Neuroscience Letters.

[3]  M. Moskowitz,et al.  L-NA-Sensitive rCBF Augmentation during Vibrissal Stimulation in Type III Nitric Oxide Synthase Mutant Mice , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  G. Bonvento,et al.  Is α-chloralose plus halothane induction a suitable anesthetic regimen for cerebrovascular research? , 1994, Brain Research.

[5]  E. Stein,et al.  Blood flow increases linearly in rat somatosensory cortex with increased whisker movement frequency , 1998, Brain Research.

[6]  L. Sokoloff,et al.  Increases in local cerebral blood flow associated with somatosensory activation are not mediated by NO. , 1994, The American journal of physiology.

[7]  A Villringer,et al.  Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics. , 1993, The American journal of physiology.

[8]  Jacques Seylaz,et al.  Effect of neuronal NO synthase inhibition on the cerebral vasodilatory response to somatosensory stimulation , 1996, Brain Research.

[9]  G. Yang,et al.  Obligatory role of NO in glutamate-dependent hyperemia evoked from cerebellar parallel fibers. , 1997, The American journal of physiology.

[10]  Ulrich Dirnagl,et al.  Nitric oxide synthase inhibition does not affect somatosensory evoked potentials in the rat , 1996, Neuroscience Letters.

[11]  M. Moskowitz,et al.  Importance of Nitric Oxide Synthase Inhibition to the Attenuated Vascular Responses Induced by Topical L-Nitroarginine during Vibrissal Stimulation , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  G. Bonvento,et al.  Local Uncoupling of the Cerebrovascular and Metabolic Responses to Somatosensory Stimulation after Neuronal Nitric Oxide Synthase Inhibition , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  Ulrich Dirnagl,et al.  Nitric oxide: a modulator, but not a mediator, of neurovascular coupling in rat somatosensory cortex. , 1999, American journal of physiology. Heart and circulatory physiology.

[14]  M. Moskowitz,et al.  Regional cerebral blood flow response to vibrissal stimulation in mice lacking type I NOS gene expression. , 1996, The American journal of physiology.