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

Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs, South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division, and Division of Geriatrics and Gerontology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas Submitted 25 January 2008 ; accepted in final form 1 May 2008 Nitric oxide (NO) participates in locally mediated vasodilation induced by increased local skin temperature (T loc ) and in sympathetically mediated vasodilation during whole body heat stress. We hypothesized that endothelial NOS (eNOS) participates in the former, but not the latter, response. We tested this hypothesis by examining the effects of the eNOS antagonist N G -amino- L -arginine ( L -NAA) on skin blood flow (SkBF) responses to increased T loc and whole body heat stress. Microdialysis probes were inserted into forearm skin for drug delivery. One microdialysis site was perfused with L -NAA in Ringer solution and a second site with Ringer solution alone. SkBF [laser-Doppler flowmetry (LDF)] and blood pressure [mean arterial pressure (MAP)] were monitored, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF ÷ MAP). In protocol 1 , T loc was controlled with LDF/local heating units. T loc initially was held at 34°C and then increased to 41.5°C. In protocol 2 , after a normothermic period, whole body heat stress was induced (water-perfused suits). At the end of both protocols, 58 mM sodium nitroprusside was perfused at both microdialysis sites to cause maximal vasodilation for data normalization. In protocol 1 , CVC at 34°C T loc did not differ between L -NAA-treated and untreated sites ( P > 0.05). Local skin warming to 41.5°C T loc increased CVC at both sites. This response was attenuated at L -NAA-treated sites ( P < 0.05). In protocol 2 , during normothermia, CVC did not differ between L -NAA-treated and untreated sites ( P > 0.05). During heat stress, CVC rose to similar levels at L -NAA-treated and untreated sites ( P > 0.05). We conclude that eNOS is predominantly responsible for NO generation in skin during responses to increased T loc , but not during reflex responses to whole body heat stress. skin blood flow; microdialysis; nitric oxide; NOS III; laser-Doppler flowmetry Address for reprint requests and other correspondence: D. L. Kellogg, Jr., Division of Geriatrics and Gerontology, Dept. of Medicine, Univ. of Texas Health Science Center at San Anto