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

Abstract

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 degrees C and then increased to 41.5 degrees 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 degrees C T(loc) did not differ between l-NAA-treated and untreated sites (P > 0.05). Local skin warming to 41.5 degrees 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.

Aerobic training increases skin perfusion by a nitric oxide mechanism in type 2 diabetes

“…15,16 The results of the present study examining dorsal foot skin perfusion concur with these observations related to the effects of localized heating on forearm skin responses. With regard to the interactions of NO and PG on skin vasodilation, in healthy humans, chronic low-dose aspirin therapy attenuates the reflex cutaneous vasodilation during whole-body heating that is mediated through both the cyclooxygenase-dependent pathway of PG formation and NO synthase-dependent mechanisms.…”

“…17 While vasodilation of skin in response to local heating is highly NO-dependent, it may also reflect the i nteraction of NO and PG. 15,18 Cutaneous acetylcholine-mediated endothelium-dependent vasodilation has been reported to be highly NO-dependent and also strongly related to the interactions of NO with prostaglandins. 18 Thus, an interaction between these two vasodilatory compounds during localized heating of dorsal foot skin to 44°C is also a possibility, albeit an untested one, in this study.…”

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

“…Figure 1 shows a representative trace of SkBF changes throughout the experiment in part 1. After dosing at the final concentration, SNP (Sigma) dissolved in sterile saline at a concentration of 56 mM was administered for 30 -40 min via microdialysis at a rate of 4 l/min, which has previously been shown to elicit maximal SkBF (20,21). As an additional study in part 1, to confirm whether the SNP dose following the administration of NE at a higher concentration can elicit maximal vasodilation, the SNP dose was performed without pretreatment of NE in six subjects.…”

Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus

“…Additionally, the initial peak has been shown to have nitric oxide and noradrenergic sympathetic nerve components (Minson et al 2001;Houghton et al 2006;Hodges et al 2008Hodges et al , 2009bTew et al 2011b). Kellogg et al (1999) determined that the plateau phase of the cutaneous vasodilator response is ∼70% dependent on NO and have recently shown that the vasodilatation in response to local skin heating is produced by endothelial NO synthase (eNOS; Kellogg et al 2008Kellogg et al , 2009.…”