Submitted on January 25, 2008
Revised on April 30, 2008
Accepted on May 1, 2008
Endothelial Nitric Oxide Synthase Control Mechanisms in the Cutaneous Vasculature of Humans In Vivo
Dean L. Kellogg, Jr.1*, Joan Liu Zhao2, and Yubo Wu2
1 University of Texas, Health Science Center
2 University of Texas Health Science Center
* To whom correspondence should be addressed. E-mail: kelloggd{at}uthscsa.edu.
Nitric oxide(NO) participates in locally mediated vasodilation induced by increased local skin temperature(Tloc) 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, NG-amino-L-arginine(LNAA) on skin blood flow(SkBF) responses to increased Tloc and whole body heat stress. Microdialysis probes were inserted into forearm skin for drug delivery. One microdialysis site was perfused with LNAA in Ringers solution, while a second site was perfused with Ringers alone. SkBF (laser-Doppler flowmetry;LDF) and blood pressure(MAP) were monitored and cutaneous vascular conductance calculated(CVC=LDF/MAP). In Protocol 1, Tloc was controlled with LDF/local heating units. Tloc 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, 58mM nitroprusside was perfused at both microdialysis sites to cause maximal vasodilation for data normalization. In protocol 1, CVC at Tloc=34°C did not differ between LNAA-treated and untreated sites(p>0.05). Local skin warming to Tloc=41.5°C increased CVC at both sites. This response was attenuated at LNAA-treated sites(p < 0.05). In protocol 2, during normothermia, CVC did not differ between LNAA-treated sites and untreated sites(p>0.05). During heat stress, CVC rose to similar levels at both LNAA-treated and untreated sites(p>0.05). We conclude that eNOS is predominantly responsible for NO generation in skin during responses to increased Tloc, but not during reflex responses to whole body heat stress.
