title: Nitric oxide inhibits cutaneous vasoconstriction to exogenous norepinephrine.
abstract: Previously, we found that nitric oxide (NO) inhibits cutaneous vasoconstrictor responsiveness evoked by whole body cooling, as well as an orthostatic stress in the heat-stressed human (Shibasaki M, Durand S, Davis SL, Cui J, Low DA, Keller DM, Crandall CG. J Physiol 585: 627-634, 2007). However, it remains unknown whether this response occurs via NO acting through presynaptic or postsynaptic mechanisms. The aim of this study was to test the hypothesis that NO is capable of impairing cutaneous vasoconstriction via postsynaptic mechanisms. Skin blood flow was monitored over two forearm sites where intradermal microdialysis membranes were previously placed. Skin blood flow was elevated four- to fivefold through perfusion of the NO donor sodium nitroprusside at one site and through perfusion of adenosine (primarily non-NO mechanisms) at a second site. Once a plateau in vasodilation was evident, increasing concentrations of norepinephrine (1 x 10(-8) to 1 x 10(-2) M) were administrated through both microdialysis probes, while the aforementioned vasodilator agents continued to be perfused. Cutaneous vascular conductance was calculated by dividing skin blood flow by mean arterial blood pressure. The administration of norepinephrine decreased cutaneous vascular conductance at both sites. However, the dose of norepinephrine at the onset of vasoconstriction (-5.9 +/- 1.3 vs. -7.2 +/- 0.7 log M norepinephrine, P = 0.021) and the concentration of norepinephrine resulting in 50% of the maximal vasoconstrictor response (-4.9 +/- 1.2 vs. -6.1 +/- 0.2 log M norepinephrine dose; P = 0.012) occurred at significantly higher norepinephrine concentrations for the sodium nitroprusside site relative to the adenosine site, respectively. These results suggested that NO is capable of attenuating cutaneous vasoconstrictor responsiveness to norepinephrine via postsynaptic mechanisms.
authors.affiliation: Department of Environmental Health, Nara Women's University, Dallas, TX, USA.
authors.forename: Manabu
authors.initials: M
authors.lastname: Shibasaki
authors.forename: David A
authors.initials: DA
authors.lastname: Low
authors.forename: Scott L
authors.initials: SL
authors.lastname: Davis
authors.forename: Craig G
authors.initials: CG
authors.lastname: Crandall
mesh_terms: D000241:Adenosine / Q000008:administration & dosage; D000328:Adult; D001808:Blood Vessels / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000008:administration & dosage; D009638:Norepinephrine / Q000008:administration & dosage*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000241:Adenosine; D009638:Norepinephrine
references.citation: J Appl Physiol (1985). 2006 May;100(5):1709-18
references.pmid: 16614368
references.citation: J Physiol. 2005 Jan 15;562(Pt 2):629-34
references.pmid: 15539401
references.citation: J Physiol. 2006 Sep 15;575(Pt 3):953-9
references.pmid: 16793901
references.citation: J Appl Physiol (1985). 2007 May;102(5):1839-43
references.pmid: 17272405
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H784-9
references.pmid: 17468334
references.citation: J Physiol. 2007 Dec 1;585(Pt 2):627-34
references.pmid: 17947310
references.citation: Trends Endocrinol Metab. 2003 Apr;14(3):114-7
references.pmid: 12670736
references.citation: J Appl Physiol (1985). 2000 Feb;88(2):467-72
references.pmid: 10658012
references.citation: J Clin Endocrinol Metab. 2000 Apr;85(4):1577-83
references.pmid: 10770200
references.citation: Am J Physiol Renal Physiol. 2001 Feb;280(2):F193-206
references.pmid: 11208594
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 May;280(5):R1494-8
references.pmid: 11294774
references.citation: J Appl Physiol (1985). 2001 Oct;91(4):1619-26
references.pmid: 11568143
references.citation: J Physiol. 2002 Apr 1;540(Pt 1):377-86
references.pmid: 11927694
references.citation: Ann N Y Acad Sci. 2002 May;962:122-30
references.pmid: 12076969
references.citation: Auton Neurosci. 2002 May 31;97(2):122-8
references.pmid: 12132645
references.citation: Endocr Rev. 2002 Oct;23(5):665-86
references.pmid: 12372846
references.citation: J Appl Physiol (1985). 2002 Dec;93(6):1947-51
references.pmid: 12391110
references.citation: J Physiol. 2003 Nov 15;553(Pt 1):281-92
references.pmid: 12949223
references.citation: Am J Physiol Heart Circ Physiol. 2004 Jan;286(1):H296-303
references.pmid: 14684362
references.citation: J Appl Physiol. 1969 Nov;27(5):673-80
references.pmid: 5360442
references.citation: Circ Res. 1974 Apr;34(4):515-24
references.pmid: 4826928
references.citation: J Invest Dermatol. 1977 Jul;69(1):154-66
references.pmid: 326990
references.citation: J Appl Physiol (1985). 1986 Nov;61(5):1613-22
references.pmid: 3536836
references.citation: Am J Hypertens. 1990 Mar;3(3):211-8
references.pmid: 2157467
references.citation: Circ Res. 1990 May;66(5):1420-6
references.pmid: 2335034
references.citation: Circ Res. 1994 Dec;75(6):1073-7
references.pmid: 7955145
references.citation: Circulation. 1995 Oct 15;92(8):2135-41
references.pmid: 7554193
references.citation: J Appl Physiol (1985). 1996 Nov;81(5):2192-8
references.pmid: 8941544
references.citation: Hypertension. 1997 Jan;29(1 Pt 2):268-73
references.pmid: 9039113
references.citation: Hypertension. 1997 Oct;30(4):957-61
references.pmid: 9336400
references.citation: J Appl Physiol (1985). 1998 Sep;85(3):824-9
references.pmid: 9729553
references.citation: J Appl Physiol (1985). 1998 Sep;85(3):830-4
references.pmid: 9729554
references.citation: J Appl Physiol (1985). 1999 Apr;86(4):1185-90
references.pmid: 10194201
references.citation: Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2576-84
references.pmid: 15271659
references.citation: J Appl Physiol (1985). 2006 Aug;101(2):492-9
references.pmid: 16614358