Almost 70 years ago the human cutaneous active vasodilator system was first described; however, its mechanisms remain unclear today. The long term goal of this project is to define the physiological mechanisms that effect cutaneous active vasodilation during thermoregulatory reflex responses to hyperthermia. This will contribute to our understanding of the role of the cutaneous circulation in adaptation to hot environments and understanding the increased morbidity and mortality of persons with limited cardiac output, including the aged and those with cardiac disease. An enhanced understanding of the cutaneous circulation may reduce mortality in the growing patient population that receives numerous pharmacological therapies that may predispose them to iatrogenic heat intolerance, heat stroke, and death. The following specific aims will be explored. 1) Determine whether bradykinin is involved in cutaneous active vasodilation during heat stress. 2) Clarify whether nitric oxide (NO) levels increase and cause cutaneous active vasodilation during heat stress or whether NO levels remain constant and functions as a permissive factor during heat stress. 3) Determine whether the nitric oxide required for cutaneous active vasodilation during heat stress is produced by endothelial nitric oxide synthase (eNOS) or by neuronal nitric oxide synthase (nNOS). 4) Determine the role of vasoactive intestinal polypeptide (VIP) in cutaneous active vasodilation during heat stress. 5) Determine the role of cAMP in cutaneous active vasodilation during heat stress. 6) Determine the role of cGMP in cutaneous active vasodilation during heat stress. Studies will be done in healthy humans. Intradermal microdialysis will be used to treat small areas of forearm skin with specific pharmacological agents to manipulate the bradykinin, nitric oxide, VIP, and second messenger systems. Laser-Doppler flowmetry will monitor skin blood flow responses during normothermia and hyperthermia at both drug-treated, experimental sites, and at adjacent untreated, control sites. In addition intradermal microdialysis will be combined with measurements of bioavailable NO by hemoglobin-trapping to define further how the NO system functions in cutaneous active vasodilation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065599-04
Application #
6615592
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Lin, Michael
Project Start
2000-09-15
Project End
2005-07-31
Budget Start
2003-08-01
Budget End
2005-07-31
Support Year
4
Fiscal Year
2003
Total Cost
$213,500
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Hodges, Gary J; Kellogg, Dean L; Johnson, John M (2015) Effect of skin temperature on cutaneous vasodilator response to the ?-adrenergic agonist isoproterenol. J Appl Physiol (1985) 118:898-903
Kellogg Jr, Dean L; Zhao, Joan L; Wu, Yubo et al. (2011) Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans. J Appl Physiol (1985) 110:1406-13
Johnson, John M; Kellogg Jr, Dean L (2010) Thermoregulatory and thermal control in the human cutaneous circulation. Front Biosci (Schol Ed) 2:825-53
Johnson, John M; Kellogg Jr, Dean L (2010) Local thermal control of the human cutaneous circulation. J Appl Physiol 109:1229-38
Kellogg Jr, Dean L; Zhao, Joan L; Wu, Yubo et al. (2010) VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans. J Appl Physiol 109:95-100
Kellogg Jr, Dean L; Zhao, Joan L; Wu, Yubo (2009) Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans. J Appl Physiol 107:1438-44
Kellogg Jr, Dean L; Zhao, Joan L; Wu, Yubo (2008) Endothelial nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo. Am J Physiol Heart Circ Physiol 295:H123-9
Kellogg Jr, D L; Hodges, G J; Orozco, C R et al. (2007) Cholinergic mechanisms of cutaneous active vasodilation during heat stress in cystic fibrosis. J Appl Physiol 103:963-8
Kellogg Jr, D L (2006) In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. J Appl Physiol 100:1709-18
Zhao, J L; Pergola, P E; Roman, L J et al. (2004) Bioactive nitric oxide concentration does not increase during reactive hyperemia in human skin. J Appl Physiol 96:628-32

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