Functional uncoupling of hemodynamic from neuronal response by inhibition of neuronal nitric oxide synthase.
The cerebrovascular coupling under neuronal nitric oxide synthase (nNOS) inhibition was investigated in alpha-chloralose anesthetized rats. Cerebral blood flow (CBF), cerebral blood volume (CBV), and blood oxygenation level dependent (BOLD) responses to electrical stimulation of the forepaw were measured before and after an intraperitoneal bolus of 7-nitroindazole (7-NI), an in vivo inhibitor of the neuronal isoform of nitric oxide synthase. Neuronal activity was measured by recording somatosensory-evoked potentials (SEPs) via intracranial electrodes. 7-Nitroindazole produced a significant attenuation of the activation-elicited CBF (P<10(-6)), CBV (P<10(-6)), and BOLD responses (P<10(-6)), without affecting the baseline perfusion level. The average DeltaCBF was nulled, while DeltaBOLD and DeltaCBV decreased to approximately 30% of their respective amplitudes before 7-NI administration. The average SEP amplitude decreased (P<10(-5)) to approximately 60% of its pretreatment value. These data describe a pharmacologically induced uncoupling between neuronal and hemodynamic responses to functional activation, and provide further support for the critical role of neuronally produced NO in the cerebrovascular coupling.
Stefanovic
Bojana
B
Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1065, USA. stefanovicb@ninds.nih.gov
Schwindt
Wolfram
W
Hoehn
Mathias
M
Silva
Afonso C
AC
D000758:Anesthesia; D018686:Anesthetics, Intravenous; D000818:Animals; D001810:Blood Volume / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002698:Chloralose; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005528:Foot / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000187:drug effects*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D007191:Indazoles; D002698:Chloralose; D052248:Nitric Oxide Synthase Type I; D010100:Oxygen; C080122:7-nitroindazole