title: The role of nitrite in neurovascular coupling.
abstract: Nitric oxide (NO), a potent vasodilator and nontraditional neurotransmitter, is an important mediator of the changes in cerebral blood flow (CBF) associated with increased neuronal activity (neurovascular coupling). In the present work, we investigated the role of NO and of its newly recognized precursor, nitrite, in neurovascular coupling using a well-established rat model of somatosensory stimulation. Biological synthesis of NO of neuronal origin was inhibited pharmacologically. Following the initial uncoupling of neuronal and hemodynamic responses to somatosensory stimulation, the NO donor sodium nitroprusside, added within the range of physiological concentrations, significantly increased, but did not fully restore the functional CBF response. In contrast, nitrite at its physiological concentration fully recovered neurovascular coupling to its original magnitude. The magnitude of the effect is, however, dose-dependent. Sub-physiological concentrations of nitrite were not enough to entirely restore neurovascular coupling and supra-physiological concentrations acted more as a local vasodilator that changed resting CBF and interfered with the functional CBF response. These results suggest that nitrite can be efficiently converted into NO and utilized to support normal cerebrovascular physiology.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. piknovab@mail.nih.gov
authors.forename: Barbora
authors.initials: B
authors.lastname: Piknova
authors.forename: Ara
authors.initials: A
authors.lastname: Kocharyan
authors.forename: Alan N
authors.initials: AN
authors.lastname: Schechter
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Silva
mesh_terms: D000758:Anesthesia; D018686:Anesthetics, Intravenous; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001808:Blood Vessels / Q000294:innervation* / Q000502:physiology*; D001831:Body Temperature; D002560:Cerebrovascular Circulation / Q000502:physiology; D002698:Chloralose; D003627:Data Interpretation, Statistical; D004569:Electroencephalography / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018686:Anesthetics, Intravenous; D020030:Nitric Oxide Donors; D009573:Nitrites; D009599:Nitroprusside; D002698:Chloralose; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I