Over 70 years ago the human cutaneous active vasodilator system (AVD) was first described; however, its mechanisms remain unclear today. The long-term goal of this project is to define the integrative 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 to understanding the increased morbidity and mortality of persons due to heat related illness in """"""""heat waves"""""""". In addition to the specific benefits to be gained in understanding human thermoregulation, this project will add greatly to our understanding of how complex neural co-transmitter systems can control the cardiovascular system. Study of the AVD co-transmitter system that controls the cutaneous vasculature in humans can be used to gain insights into how co-transmitter neural control systems work. Gaining such knowledge directly from human beings in vivo could not be accomplished in any other human tissue, in vivo, without significant risk. The following specific aims will be explored: 1) To determine whether cutaneous AVD during heat stress is atropine-sensitive in cystic fibrosis patients. 2) To determine whether activation of VPAC1 and/or PAC1 receptors mediate cutaneous active vasodilation during hyperthermia. 3) To resolve whether muscarinic receptor activation by endogenous acetylcholine release contributes to increased nitric oxide levels during cutaneous active vasodilation in heat stress. 4) To resolve whether the nitric oxide required for cutaneous active vasodilation is produced by endothelial nitric oxide synthase (eNOS) and/or by neuronal nitric oxide synthase (nNOS) during heat stress. 5) To define the role of cAMP in cutaneous active vasodilation during heat stress. 6) To define the role of cGMP in cutaneous active vasodilation during heat stress. Studies will be done in healthy humans and patients with cystic fibrosis. Intradermal microdialysis will be used to treat small areas of forearm skin with specific pharmacological agents to manipulate the cholinergic, neuropeptidergic, nitric oxide, 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 NO-selective amperometric electrode to define further how the NO system functions in cutaneous active vasodilation.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-CICS (01))
Program Officer
Lin, Michael
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University of Texas Health Science Center San Antonio
Internal Medicine/Medicine
Schools of Medicine
San Antonio
United States
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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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