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1 Nara Women's University
2 Institute for Exercise and Environmental Medicine
3 University of Texas Southwestern Medical Center at Dallas
4 Presbyterian Hospital of Dallas
* To whom correspondence should be addressed. E-mail: craigcrandall{at}texashealth.org.
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. However it remains unknown whether this response occurs via NO acting through pre-synaptic or post-synaptic mechanisms. The aim of this study was to test the hypothesis that NO is capable of impairing cutaneous vasoconstriction via post-synaptic mechanisms. Skin blood flow was monitored over two forearm sites where intradermal microdialysis membranes were previously placed. Skin blood flow was elevated 4 to 5 fold through perfusion of the NO donor sodium nitroprusside (SNP) 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 (CVC) was calculated by dividing skin blood flow by mean arterial blood pressure. The administration of norepinephrine decreased CVC 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 SNP site relative to the adenosine site, respectively. These results suggested that NO is capable of attenuating cutaneous vasoconstrictor responsiveness to norepinephrine via post-synaptic mechanisms.
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