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J Physiol Volume 586, Number 3, 847-857, February 1, 2008 DOI: 10.1113/jphysiol.2007.144642
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CARDIOVASCULAR

Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo

Dean L. Kellogg, Jr1,2, Joan L. Zhao2 and Yubo Wu2

1 Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs, South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division
2 Division of Geriatrics and Gerontology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA

The physiological roles of constituitively expressed nitric oxide synthase (NOS) isoforms in humans, in vivo, are unknown. Cutaneous vasodilatation during both central nervous system-mediated, thermoregulatory reflex responses to whole-body heat stress and during peripheral axon reflex-mediated, local responses to skin warming in humans depend on nitric oxide (NO) generation by constituitively expressed NOS of uncertain isoform. We hypothesized that neuronal NOS (nNOS, NOS I) effects cutaneous vasodilatation during whole-body heat stress, but not during local skin warming. We examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) administered by intradermal microdialysis on vasodilatation induced by whole-body heat stress or local skin warming. Skin blood flow (SkBF) was monitored by laser–Doppler flowmetry (LDF). Blood pressure (MAP) was monitored and cutaneous vascular conductance calculated (CVC = LDF/MAP). In protocol 1, whole-body heat stress was induced with water-perfused suits. In protocol 2, local skin warming was induced through local warming units at LDF sites. At the end of each protocol, 56 mM sodium nitroprusside was perfused at microdialysis sites to raise SkBF to maximal levels for data normalization. 7-NI significantly attenuated CVC increases during whole-body heat stress (P < 0.05), but had no effect on CVC increases induced by local skin warming (P > 0.05). These diametrically opposite effects of 7-NI on two NO-dependent processes verify selective nNOS antagonism, thus proving that the nNOS isoform affects NO increases and hence vasodilatation during centrally mediated, reflex responses to whole-body heat stress, but not during locally mediated, axon reflex responses to local skin warming. We conclude that the constituitively expressed nNOS isoform has distinct physiological roles in cardiovascular control mechanisms in humans, in vivo.

(Received 5 September 2007; accepted after revision 22 November 2007; first published online 29 November 2007)
Corresponding author D. L. Kellogg Jr: Division of Geriatrics and Gerontology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229, USA. Email: kelloggd{at}uthscsa.edu




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