Endurance training enhances vasodilation induced by nitric oxide in human skin.

Endurance training modifies the thermoregulatory control of skin blood flow, as manifested by a greater augmentation of skin perfusion for the same increase in core temperature in athletes, in comparison with sedentary subjects. In this study, we tested the hypothesis that a component of this adaptation might reside in a higher ability of cutaneous blood vessels to respond to vasodilatory stimuli. We recruited healthy nonsmoking males, either endurance trained or sedentary, in two different age ranges (18-35 y and >50 y). Skin blood flow was measured in the forearm skin, using a laser Doppler imager, allowing to record the vasodilatory responses to the following stimuli: iontophoresis of acetylcholine (an endothelium-dependent vasodilator), iontophoresis of sodium nitroprusside (a nitric oxide donor), and release of a temporary interruption of arterial inflow (reactive hyperemia). There was no effect of training on reactive hyperemia or the response to acetylcholine. In contrast, the increase in perfusion following the iontophoresis of sodium nitroprusside, expressed in perfusion units, was larger in trained than in sedentary subjects (younger: 398 +/- 54 vs 350 +/- 87, p < 0.05; older 339 +/- 72 vs 307 +/- 66, p < 0.05). In conclusion, endurance training enhances the vasodilatory effects of nitric oxide in the human dermal microcirculation, at least in forearm skin. These observations have considerable physiologic interest in view of recent data indicating that nitric oxide mediates in part the cutaneous vasodilation induced by heat stress in humans. Therefore, the augmentation of nitric oxide bioactivity in the dermal microcirculation might be one mechanism whereby endurance training modifies the thermoregulatory control of skin blood flow.

Blunted vasodilatory responses in the cutaneous microcirculation of cigarette smokers.

OBJECTIVE: The present study was undertaken to investigate whether chronic smoking alters the vasodilatory capacity in the microcirculation. METHODS: We assessed, in habitual cigarette smokers, the forearm skin blood flow response to iontophoretically applied acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside. Postocclusive forearm reactive hyperemia was also explored. The skin blood flow responses were determined with a laser-Doppler flowmeter that allowed us to scan the surface after acetylcholine and sodium nitroprusside application. RESULTS: Forty healthy male volunteers were included. Twenty subjects were aged 20 to 35 years and 20 subjects were aged 40 to 60 years. We studied the following 4 groups of 10 subjects each: group 1, younger smokers (mean of 7.2 pack-years); group 2, older smokers (mean of 30 pack-years); group 3, younger nonsmokers; and group 4, older nonsmokers. On the day of the experiment, the subjects of groups 1 and 2 were asked to smoke at least 15 cigarettes from the morning until the afternoon, when the experiments were performed. No significant difference in the studied parameters was observed between younger smokers and younger nonsmokers. In older smokers, however, both acetylcholine- and sodium nitroprusside-induced skin blood flow increases were significantly attenuated in comparison with nonsmokers. Heart rate also was significantly blunted by long-term cigarette smoking in older subjects. CONCLUSION: These data show that the vasodilatory response of the skin microvasculature is impaired in subjects who have smoked cigarettes for many years. This abnormality involves both endothelium-dependent and endothelium-independent responses.

Endothelium-dependent vasodilation in the skin microcirculation of patients with septic shock.

The evidence for endothelial dysfunction in sepsis is mostly restricted to animal models. We investigated endothelial function in the skin microcirculation of eight patients hospitalized for septic shock in an intensive care unit (ICU). All patients required adrenergic support. Twelve hemodynamically stable ICU patients without sepsis who did not receive any vasoactive medication were used as controls. The two groups were of similar age and sex ratio. For additional reference, 16 healthy, nonsmoking subjects matched for age and sex to the first two groups were also studied. The evaluation of endothelial function was based on the comparison of skin blood flow responses to iontophoretically applied acetylcholine (Ach, an endothelium-dependent vasodilator) and sodium nitroprusside (SNP, an endothelium-independent vasodilator). Skin blood flow was measured on the volar face of the forearm using laser Doppler imaging. Before application of Ach or SNP, the mean baseline skin blood flow was below 100 perfusion units (PU) in all subjects and did not differ between groups. The maximal increase in blood flow elicited by both agents was significantly depressed in the patients with sepsis (Ach: 167 +/- 63 PU; SNP: 138 +/- 34 PU, mean +/- SD) compared with the ICU control patients (Ach: 291 +/- 135 PU, P < 0.05; SNP: 261 +/- 121 PU, P < 0.01) and the healthy, nonsmoking groups (Ach: 336 +/- 98 PU, P < 0.01; SNP: 304 +/- 81 PU, P < 0.01). The ratio of responses to Ach and SNP did not significantly differ between groups (septic: 1.22 +/- 0.40; ICU control 1.18 +/- 0.46, healthy, nonsmoking 1.12 +/- 0.24, P = 0.86). Thus, sepsis was not associated with a selective depression of the endothelium-dependent response. These results suggest that the capacity of the endothelium to produce signals for vasorelaxation remains intact in the skin microcirculation of patients with septic shock.

Acetylcholine-induced vasodilation and reactive hyperemia are not affected by acute cyclo-oxygenase inhibition in human skin.

OBJECTIVE: To examine whether prostaglandins are involved in endothelium-dependent vasodilatory responses of the skin microcirculation. METHODS: Twenty-three young male volunteers were studied on 2 different days 1-3 weeks apart. On each experimental day the forearm skin blood flow response to iontophoretically applied acetylcholine (Ach, an endothelium-dependent vasodilator) was determined with laser Doppler imaging following the intravenous administration of either the cyclo-oxygenase inhibitor lysine acetylsalicylate (L-AS), 900 mg, or the oral intake of indomethacin, 75 mg. Acetylcholine was iontophoresed both in presence and in absence of surface anesthesia. In some subjects, the effects of L-AS on skin reactive hyperemia were also assessed. RESULTS: Acute cyclo-oxygenase inhibition with either drug influenced neither the skin blood flow response to 4 different doses of Ach (0.28, 1.4, 7, and 14 mC/cm2) nor reactive hyperemia. The peak vasodilatory response to Ach was significantly increased by skin anesthesia, regardless of whether the subjects received the cyclo-oxygenase inhibitor or not. For example, the mean response (+/-SD) to the largest dose of Ach (tested in 6 subjects, expressed in perfusion units) were as follows: in absence of anesthesia: L-AS 339 +/- 105, placebo 344 +/- 68; with anesthesia: L-AS 453 +/- 76, placebo 452 +/- 65 (p <.01 for effect of anesthesia). CONCLUSIONS: These data give no support for a contribution of prostaglandins to acetylcholine-induced vasodilation or to reactive hyperemia in the skin microcirculation. In this vascular bed, local anesthesia seems to amplify acetylcholine-induced vasodilation via a prostaglandin-independent mechanism.