The rise in skin blood flow where humans are exposed to whole body heating is mediated by an active vasodilator reflex that is unique in humans. Although a number of vasoactive substances have been identified that may be involved in active cutaneous vasodilation, the identity of the putative vasodilator is not known. Of these potential vasodilator substances, a role for vasoactive intestinal peptide (VIP) and adenosine in active cutaneous vasodilation appears likely and are specifically targeted in the proposed studies. A portion of the active vasodilator reflex is dependent on NO, but the exact role of NO in this response is unclear. Animal research suggests that NO may act synergistically with the unknown vasodilator to elicit full expression of the active vasodilator response, but that NO is not directly involved. These mechanisms of active cutaneous vasodilation have not been investigated in humans. Thus, the overall goal of this application is to systematically investigate the mechanisms that underlie active cutaneous vasodilation in the skin of humans during whole body heating. This overall goal will be met by addressing the following specific questions: 1) What are the roles of cAMP- and cGMP-dependent pathways in active cutaneous vasodilation? 2) Does cGMP augment cAMP-mediated active vasodilation in the skin of humans during whole body heating? 3) Is the cGMP-mediated portion of active cutaneous vasodilation the same or different as the NO-mediated portion of active cutaneous vasodilation? 4) Does NO act synergistically with the unknown vasodilator substance to allow full expression of active cutaneous vasodilation during whole body heat stress in humans? 5) What is the role of VIP in active cutaneous vasodilation in humans? 6) What is the role of adenosine in active cutaneous vasodilation in humans? These questions will be investigated in humans using state-of-the-art techniques. The findings from these studies will significantly advance our understanding of the control of skin blood flow in humans, and will lead to future studies directed at investigating the diminished thermoregulatory capacity in the elderly and patient populations.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL070928-03
Application #
6729201
Study Section
Special Emphasis Panel (ZRG1-ALTX-1 (01))
Program Officer
Goldman, Stephen
Project Start
2002-05-02
Project End
2006-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
3
Fiscal Year
2004
Total Cost
$181,264
Indirect Cost
Name
University of Oregon
Department
Miscellaneous
Type
Schools of Arts and Sciences
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403
Wong, Brett J; Minson, Christopher T (2011) Altered thermal hyperaemia in human skin by prior desensitization of neurokinin-1 receptors. Exp Physiol 96:599-609
Minson, Christopher T (2010) Thermal provocation to evaluate microvascular reactivity in human skin. J Appl Physiol 109:1239-46
Torgrimson, Britta N; Meendering, Jessica R; Miller, Nicole P et al. (2009) Endothelial function, endothelin-1, and fibrinogen in young women using the vaginal contraceptive ring. Fertil Steril 92:441-7
Lorenzo, Santiago; Minson, Christopher T (2007) Human cutaneous reactive hyperaemia: role of BKCa channels and sensory nerves. J Physiol 585:295-303
Cracowski, Jean-Luc; Lorenzo, Santiago; Minson, Christopher T (2007) Effects of local anaesthesia on subdermal needle insertion pain and subsequent tests of microvascular function in human. Eur J Pharmacol 559:150-4
Houghton, Belinda L; Meendering, Jessica R; Wong, Brett J et al. (2006) Nitric oxide and noradrenaline contribute to the temperature threshold of the axon reflex response to gradual local heating in human skin. J Physiol 572:811-20
Wong, Brett J; Williams, Sarah J; Minson, Christopher T (2006) Minimal role for H1 and H2 histamine receptors in cutaneous thermal hyperemia to local heating in humans. J Appl Physiol 100:535-40
Cracowski, Jean-Luc; Minson, Christopher T; Salvat-Melis, Muriel et al. (2006) Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci 27:503-8
Wong, Brett J; Minson, Christopher T (2006) Neurokinin-1 receptor desensitization attenuates cutaneous active vasodilatation in humans. J Physiol 577:1043-51
Wong, Brett J; Tublitz, Nathan J; Minson, Christopher T (2005) Neurokinin-1 receptor desensitization to consecutive microdialysis infusions of substance P in human skin. J Physiol 568:1047-56

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