Nitric oxide inhibits cutaneous vasoconstriction to exogenous norepinephrine.
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.
Shibasaki
Manabu
M
Department of Environmental Health, Nara Women's University, Dallas, TX, USA.
Low
David A
DA
Davis
Scott L
SL
Crandall
Craig G
CG
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
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000241:Adenosine; D009638:Norepinephrine
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