Nitric oxide synthase is critical in mediating basal forebrain regulation of cortical cerebral circulation.
This study sought to determine whether the activity of nitric oxide synthase (NOS) is an important physiological link required to mediate increases in cortical cerebral blood flow (CBF) elicited by electrical microstimulation of the basal forebrain (BF). Changes in cortical CBF were assessed in urethane anesthetized rats using laser-Doppler flowmetry. Microstimulation of the BF elicited stimulus-locked increases in CBF that were dependent on frequency and current intensity (up to 280% of control at 50 Hz). Infusion of the potent NOS inhibitor NG-nitro-L-arginine (L-NNA) resulted in significant dose-related reductions in the BF-elicited response at 50 Hz (3.75-60 mg/kg, i.v.), significant elevation in resting mean arterial pressure (MAP) from 106 to 160 mmHg, and modest 21% reductions in resting CBF. The stereoisomer NG-nitro-D-arginine (D-NNA) was without any effect on CBF, although at higher concentrations MAP was elevated to levels comparable to those obtained with L-NNA. Infusion of arginase was also without effect on resting or BF-elicited CBF responses. In contrast, L-arginine (100-400 mg/kg, i.v.) significantly potentiated the BF-elicited response up to an additional 38%, without affecting resting CBF or MAP. This study suggests that NO, or a related nitroso precursor formed by NOS, has a critical role in mediating regulation of cortical CBF by BF neurons.
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D017078:Laser-Doppler Flowmetry; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D016548:Prosencephalon / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques
D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases