title: Neuronal-derived nitric oxide and somatodendritically released vasopressin regulate neurovascular coupling in the rat hypothalamic supraoptic nucleus.
abstract: The classical model of neurovascular coupling (NVC) implies that activity-dependent axonal glutamate release at synapses evokes the production and release of vasoactive signals from both neurons and astrocytes, which dilate arterioles, increasing in turn cerebral blood flow (CBF) to areas with increased metabolic needs. However, whether this model is applicable to brain areas that also use less conventional neurotransmitters, such as neuropeptides, is currently unknown. To this end, we studied NVC in the rat hypothalamic magnocellular neurosecretory system (MNS) of the supraoptic nucleus (SON), in which dendritic release of neuropeptides, including vasopressin (VP), constitutes a key signaling modality influencing neuronal and network activity. Using a multidisciplinary approach, we investigated vasopressin-mediated vascular responses in SON arterioles of hypothalamic brain slices of Wistar or VP-eGFP Wistar rats. Bath-applied VP significantly constricted SON arterioles (Δ-41 ± 7%) via activation of the V1a receptor subtype. Vasoconstrictions were also observed in response to single VP neuronal stimulation (Δ-18 ± 2%), an effect prevented by V1a receptor blockade (V2255), supporting local dendritic VP release as the key signal mediating activity-dependent vasoconstrictions. Conversely, osmotically driven magnocellular neurosecretory neuronal population activity leads to a predominant nitric oxide-mediated vasodilation (Δ19 ± 2%). Activity-dependent vasodilations were followed by a VP-mediated vasoconstriction, which acted to limit the magnitude of the vasodilation and served to reset vascular tone following activity-dependent vasodilation. Together, our results unveiled a unique and complex form of NVC in the MNS, supporting a competitive balance between nitric oxide and activity-dependent dendritic released VP, in the generation of proper NVC responses.
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Wenting
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Javier E
authors.initials: JE
authors.lastname: Stern
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, Georgia 30912 jfilosa@gru.edu.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Filosa
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D003712:Dendrites / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000502:physiology; D009490:Neurosecretory Systems / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017483:Receptors, Vasopressin / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; C582098:V1a vasopressin receptor, rat; D001127:Arginine Vasopressin; D009569:Nitric Oxide; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-
keywords: arteriole; dendrite; hypothalamus; neurovascular; nitric oxide; vasopressin
references.citation: Circ Res. 2004 Nov 12;95(10):e73-81
references.pmid: 15499024
references.citation: J Physiol. 1980 Jul;304:405-14
references.pmid: 7441542
references.citation: Nat Rev Neurosci. 2006 Feb;7(2):126-36
references.pmid: 16429122
references.citation: Nat Neurosci. 2006 Nov;9(11):1397-1403
references.pmid: 17013381
references.citation: Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2855-63
references.pmid: 18456724
references.citation: Neuroscience. 1984 Nov;13(3):769-79
references.pmid: 6527778
references.citation: Nat Neurosci. 2003 Jan;6(1):43-50
references.pmid: 12469126
references.citation: Nature. 1986 Aug 21-27;322(6081):738-40
references.pmid: 3748154
references.citation: Brain Res. 2000 May 19;865(1):27-34
references.pmid: 10814730
references.citation: Stroke. 2009 Apr;40(4):1451-7
references.pmid: 19246694
references.citation: Neuroscience. 1993 Nov;57(2):473-82
references.pmid: 7906874
references.citation: Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H205-13
references.pmid: 15331368
references.citation: Horm Metab Res. 2010 Jan;42(1):56-60
references.pmid: 19672816
references.citation: J Neurosci. 1984 Oct;4(10):2650-7
references.pmid: 6491728
references.citation: Nature. 2004 Sep 9;431(7005):195-9
references.pmid: 15356633
references.citation: J Neuroendocrinol. 1998 Dec;10(12):881-95
references.pmid: 9870745
references.citation: J Neurosci. 2006 Mar 15;26(11):2862-70
references.pmid: 16540563
references.citation: J Physiol. 2005 Feb 1;562(Pt 3):725-44
references.pmid: 15550458
references.citation: J Physiol. 2004 Jun 15;557(Pt 3):949-60
references.pmid: 15107473
references.citation: J Neurosci. 2006 Jun 28;26(26):6997-7006
references.pmid: 16807329
references.citation: Glia. 2001 Apr 1;34(1):27-38
references.pmid: 11284017
references.citation: J Appl Physiol (1985). 2006 Mar;100(3):1059-64
references.pmid: 16467392
references.citation: Prog Brain Res. 1998;119:59-76
references.pmid: 10074781
references.citation: Brain Res. 1991 Sep 6;558(2):191-6
references.pmid: 1782541
references.citation: Neuroscience. 2013 Oct 10;250:70-9
references.pmid: 23850590
references.citation: J Neurosci. 1998 May 15;18(10):3548-53
references.pmid: 9570786
references.citation: Brain Res Bull. 1985 Feb;14(2):123-32
references.pmid: 2986791
references.citation: Neurosci Res. 2007 Oct;59(2):160-71
references.pmid: 17655958
references.citation: Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H423-33
references.pmid: 12063317
references.citation: J Neurosci. 2003 May 15;23(10):4228-39
references.pmid: 12764111
references.citation: J Cereb Blood Flow Metab. 1993 Mar;13(2):285-90
references.pmid: 8436620
references.citation: Anat Embryol (Berl). 2001 Apr;203(4):309-21
references.pmid: 11396857
references.citation: J Appl Physiol (1985). 2006 Jan;100(1):328-35
references.pmid: 16357086
references.citation: Neuron. 1997 Oct;19(4):903-12
references.pmid: 9354336
references.citation: Neuroscience. 1999;92(1):47-60
references.pmid: 10392829
references.citation: Prog Neurobiol. 1995 Nov-Dec;47(4-5):291-339
references.pmid: 8966209
references.citation: Nat Methods. 2012 Mar;9(3):273-6
references.pmid: 22266543
references.citation: Free Radic Biol Med. 2014 Aug;73:421-9
references.pmid: 24887095
references.citation: Acta Physiol Scand. 1986 Sep;128(1):23-31
references.pmid: 3766172
references.citation: J Neurosci. 1998 Mar 1;18(5):1879-85
references.pmid: 9465012
references.citation: J Neuroendocrinol. 2008 Jun;20(6):677-86
references.pmid: 18601689
references.citation: J Physiol. 1989 Oct;417:263-77
references.pmid: 2621593
references.citation: Brain Res Bull. 1993;32(3):207-10
references.pmid: 8374798
references.citation: Neuroendocrinology. 1993 Dec;58(6):637-45
references.pmid: 8127393
references.citation: J Physiol. 1995 May 1;484 ( Pt 3):743-53
references.pmid: 7623289
references.citation: Neurochem Res. 1997 Jul;22(7):825-9
references.pmid: 9232635
references.citation: Endocrinology. 1994 Mar;134(3):1011-7
references.pmid: 7509733
references.citation: Nat Neurosci. 2007 Nov;10(11):1369-76
references.pmid: 17965657
references.citation: Endocrinology. 2005 Jan;146(1):406-13
references.pmid: 15375027
references.citation: Brain Res. 1985 Dec 30;361(1-2):225-32
references.pmid: 4084795
references.citation: J Neurosurg. 1992 Sep;77(3):424-31
references.pmid: 1506890
references.citation: J Neurosci. 2014 Apr 30;34(18):6201-13
references.pmid: 24790191
references.citation: Brain Res. 1992 Aug 14;588(1):75-83
references.pmid: 1393572
references.citation: Cardiovasc Res. 2011 Nov 1;92(2):348-57
references.pmid: 21831995
references.citation: Nat Neurosci. 2006 Feb;9(2):260-7
references.pmid: 16388306
references.citation: J Neurosci. 2001 Oct 1;21(19):7841-7
references.pmid: 11567075
references.citation: J Neurosci. 2004 Oct 13;24(41):8940-9
references.pmid: 15483113
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2001 Apr;363(4):369-75
references.pmid: 11330329
references.citation: Nature. 2010 Nov 11;468(7321):232-43
references.pmid: 21068832
references.citation: Eur J Pharmacol. 1999 Jul 2;376(1-2):45-51
references.pmid: 10440088
references.citation: Brain Res Bull. 1992 Apr;28(4):599-603
references.pmid: 1617442
references.citation: J Neuroendocrinol. 1992 Aug;4(4):377-80
references.pmid: 21554620
references.citation: J Neurosci Res. 2010 May 1;88(6):1364-73
references.pmid: 19938175
references.citation: Endocrinology. 2008 Sep;149(9):4279-88
references.pmid: 18483147
references.citation: J Comp Neurol. 1980 Dec 1;194(3):555-70
references.pmid: 7451682
references.citation: PLoS Comput Biol. 2013;9(8):e1003187
references.pmid: 23966850
references.citation: J Physiol. 2012 Apr 1;590(Pt 7):1757-70
references.pmid: 22310311
references.citation: Neuron. 2013 Jun 19;78(6):1036-49
references.pmid: 23791197
references.citation: Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7797-801
references.pmid: 1715581
references.citation: Endocrinology. 2007 Feb;148(2):479-89
references.pmid: 17082256
references.citation: Neuroscience. 1986 Mar;17(3):679-86
references.pmid: 2422593
references.citation: Eur J Neurosci. 1997 Dec;9(12):2532-40
references.pmid: 9517458