Tzu Chi Medical Journal
Volume 21, Issue 1 , Pages 1-5, March 2009

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

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

Received 15 October 2008; received in revised form 20 November 2008; accepted 1 December 2008.

Article Outline

Abstract 

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.

Keywords:  Autonomic nerve , Blood–brain barrier , Cerebral blood flow , Cerebral vasodilation , Nitrergic nerve

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Toda N . Non-adrenergic, non-cholinergic innervation in monkey and human cerebral arteries . Br J Pharmacol . 1981;72:281–283
  2. Feelisch M , te Poel M , Zamora R , Deussen A , Moncada S . Understanding the controversy over the identity of EDRF . Nature . 1994;368:62–65
  3. Okamura T , Fujioka H , Ayajiki K , Toda N . Modifications by superoxide-generating agent, neurotransmitters and neuromodulators of nitroxidergic nerve function in monkey cerebral arteries . J Pharmacol Exp Ther . 1998;286:1321–1325
  4. Toda N , Okamura T . Nitroxidergic nerve: regulation of vascular tone and blood flow in the brain . J Hypertens . 1996;14:423–434
  5. Toda N , Okamura T . Modification by L-NG-monomethyl arginine (L-NMMA) of the response to nerve stimulation in isolated dog mesenteric and cerebral arteries . Jpn J Pharmacol . 1990;52:170–173
  6. Toda N , Okamura T . Mechanism underlying the response to vasodilator nerve stimulation in isolated dog and monkey cerebral arteries . Am J Physiol . 1990;259:H1511–H1517
  7. Toda N , Ayajiki K , Yoshida K , Kimura H , Okamura T . Impairment by damage of the pterygopalatine ganglion of nitrox-idergic vasodilator nerve function in canine cerebral and retinal arteries . Circ Res . 1993;72:206–213
  8. Dawson TM , Bredt DS , Fotuhi M , Hwang PM , Snyder SH . Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues . Proc Natl Acad Sci USA . 1991;88:7797–7801
  9. Nozaki K , Moskowitz MA , Maynard KI , et al.   Possible origins and distribution of immunoreactive nitric oxide synthase-containing nerve fibers in cerebral arteries . J Cereb Blood Flow Metab . 1993;13:70–79
  10. Toda N , Ayajiki K , Tanaka T , Okamura T . Preganglionic and postganglionic neurons responsible for cerebral vasodilation mediated by nitric oxide in anesthetized dogs . J Cereb Blood Flow Metab . 2000;20:700–708
  11. Toda N , Tanaka T , Ayajiki K , Okamura T . Cerebral vasodil-atation induced by stimulation of the pterygopalatine ganglion and greater petrosal nerve in anesthetized monkeys . Neuroscience . 2000;96:393–398
  12. Ayajiki K , Fujioka H , Shinozaki K , Okamura T . Effects of capsaicin and nitric oxide synthase inhibitor on increase in cere bral blood flow induced by sensory and parasym-pathetic nerve stimulation in the rat . J Appl Physiol . 2005;98:1792–1798
  13. Toda N , Okamura T . The pharmacology of nitric oxide in the peripheral nervous system of blood vessels . Pharmacol Rev . 2003;55:271–324
  14. Yarnitsky D , Gross Y , Lorian A , et al.   Blood-brain barrier opened by stimulation of the parasympathetic sphenopala-tine ganglion: a new method for macromolecule delivery to the brain . J Neurosurg . 2004;101:303–309
  15. Yarnitsky D , Gross Y , Lorian A , et al.   Increased BBB permeability by parasympathetic sphenopalatine ganglion stimulation in dogs . Brain Res . 2004;1018:236–240
  16. Fellner F , Lungenschmid K , Fellner C , Bohm-Jurkovic H , Bautz W . Experiences with gadodiamide, a non-ionic contrast agent, in MRI of brain metastases . Rontgenpraxis . 1998;51:203–211
  17. Koketsu N , Moskowitz MA , Kontos HA , Yokota M , Shimizu T . Chronic parasympathetic sectioning decreases regional cerebral blood flow during hemorrhagic hypotension and increases infarct size after middle cerebral artery occlusion in spontaneously hypertensive rats . J Cereb Blood Flow Metab . 1992;12:613–620
  18. Dalkara T , Yoshida T , Irikura K , Moskowitz MA . Dual role of nitric oxide in focal cerebral ischemia . Neuropharmacology . 1994;33:1447–1452
  19. Saito A , Handa J , Toda N . Reactivity to vasoactive agents of canine basilar arteries exposed to experimental sub-arachnoid hemorrhage . Surg Neurol . 1991;35:461–467
  20. Toda N , Kawakami M , Yoshida K . Constrictor action of oxy-hemoglobin in monkey and dog basilar arteries in vivo and in vitro . Am J Physiol . 1991;260:H420–H425
  21. Toda N , Ayajiki K , Okamura T . Neural mechanism underlying basilar arterial constriction by intracisternal L-NNA in anesthetized dogs . Am J Physiol . 1993;265:H103–H107
  22. Okamura T , Ayajiki K , Toda N . Basilar arterial constriction caused by intracisternal NG-nitro-L-arginine in anesthetized monkeys . Cardiovasc Res . 1995;30:663–667
  23. Pluta RM , Dejam A , Grimes G , Gladwin MT , Oldfield EH . Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage . JAMA . 2005;293:1477–1484
  24. Iversen HK , Olesen J , Tfelt-Hansen P . Intravenous nitro-glycerin as an experimental model of vascular headache. Basic characteristics . Pain . 1989;38:17–24
  25. Lassen LH , Ashina M , Christiansen I , Ulrich V , Olesen J . Nitric oxide synthase inhibition in migraine . Lancet . 1997;349:401–402
  26. Ayajiki K , Fujioka H , Noda K , Okamura T , Toda N . Modifications by sumatriptan and acetylcholine of nitric oxide-mediated neurogenic dilatation in dog cerebral arteries . Eur J Pharmacol . 2001;420:67–72
  27. Ayajiki K , Okamura T , Toda N . Flunarizine, an anti-migraine agent, impairs nitroxidergic nerve function in cerebral arteries . Eur J Pharmacol . 1997;329:49–53
  28. Sanders M , Zuurmond WW . Efficacy of sphenopalatine ganglion blockade in 66 patients suffering from cluster headache: a 12- to 70-month follow-up evaluation . J Neurosurg . 1997;87:876–880
  29. Toda N . Nitroxidergic nerve in cranial arteries . In:  Olesen J ,  Edvinsson L editor. Headache Pathogenesis: Monoamines, Neuropeptides, Purines and Nitric Oxide . Philadelphia: Lippincott-Raven; 1997;p. 241–245

PII: S1016-3190(09)60001-X

doi:10.1016/S1016-3190(09)60001-X

Tzu Chi Medical Journal
Volume 21, Issue 1 , Pages 1-5, March 2009

Article Tools