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Nitrergic Control of Cerebral Vascular Tone and Blood Flow, and a Possible Blood–Brain Barrier Function

Kazuhide Ayajiki, Takumi Tamayama, Kazuya Shinozaki, Tomio Okamura 

Department of Pharmacology, Shiga University of Medical Science, Otsu, Japan

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Neural control of vascular tone is important for the maintenance of circulatory homeostasis. Neurogenic vascular relaxation is obtained not only by the inhibition of constrictor nerves, but also by the stimulation of dilator nerves. We have reported that the vasodilator nerve innervating the cerebral artery is nitrergic in nature. In anesthetized animals, electrical stimulation (ES) of a pterygopalatine ganglion (PPG) or a greater petrosal nerve (GPN) only dilated cerebral arteries on the stimulated side. Nitric oxide (NO) synthase inhibitors abolished this dilation. Surgical denervation at the PPG instantly produced cerebroarterial constriction. In rats, ES of the nerve bundles from the PPG significantly increased cerebral blood flow, which was inhibited by NO synthase inhibitors. After systemic infusion of FITC (fluorescence)-dextran (10 kD) in anesthetized dogs, ES was applied to one side of the PPG. The fluorescent intensity in certain areas of the brain was higher on the stimulated side. Similar findings were obtained histochemically. T1-weighted MRI enhanced by gadolinium-DTPA during the GPN-stimulation in monkeys showed higher signal intensities in certain brain regions on the stimulated side. These findings suggest that nitrergic nerves tonically dilate the cerebral artery to maintain the cerebral circulation and may play a role in the regulation of blood–brain barrier permeability.


Autonomic nerve; Blood–brain barrier; Cerebral blood flow; Cerebral vasodilation; Nitrergic nerve


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