-Investigators report that local heat causes an increase in skin blood flow consisting of two phases. The first is solely sensory neural, and the second is nitric oxide mediated. We hypothesize that mechanisms behind these two phases are causally linked by shear stress. Because microvascular blood flow, endothelial shear stress, and vessel diameters cannot be measured in humans, bat wing arterioles (26.6 Ϯ 0.3, 42.0 Ϯ 0.4, and 58.7 Ϯ 2.2 m) were visualized noninvasively on a transparent heat plate via intravital microscopy. Increasing plate temperature from 25 to 37°C increased flow in all three arterial sizes (137.1 Ϯ 0.3, 251.9 Ϯ 0.5, and 184.3 Ϯ 0.6%) in a biphasic manner. With heat, diameter increased in large arterioles (n ϭ 6) by 8.7 Ϯ 0.03% within 6 min, medium arterioles (n ϭ 8) by 19.7 Ϯ 0.5% within 4 min, and small arterioles (n ϭ 8) by 31.6 Ϯ 2.2% in the first minute. Lidocaine (0.2 ml, 2% wt/vol) and N G -nitro-L-arginine methyl ester (0.2 ml, 1% wt/vol) were applied topically to arterioles (ϳ40 m) to block sensory nerves, modulate shear stress, and block nitric oxide generation. Local heat caused only a 10.4 Ϯ 5.5% increase in diameter with neural blockade (n ϭ 8) and only a 7.5 Ϯ 4.1% increase in diameter when flow was reduced (n ϭ 8), both significantly lower than control (P Ͻ 0.001). Diameter and flow increases were significantly reduced with N G -nitro-L-arginine methyl ester application (P Ͻ 0.05). Our novel thermoregulatory animal model illustrates 1) regulation of shear stress, 2) a nonneural component of the first phase, and 3) a shear-mediated second phase. The time course of dilation suggests that early dilation of small arterioles increases flow and enhances second-phase dilation of the large arterioles. nitric oxide; in vivo; shear stress HUMAN SKIN RESPONDS TO LOCAL temperature increases with a biphasic increase in skin blood flow (SkBF). Within the first few minutes after the local application of heat, SkBF reaches a peak and then begins to decline. Three to five minutes after heating, SkBF reaches a nadir and then increases once again (8,16,26). The second slower and more sustained response typically rises above the initial peak value. Typically, SkBF is measured noninvasively in human subjects using laser Doppler flowmetry (LDF), which ensures that the complex interaction of thermoregulatory mechanisms controlling vascular responses remains intact. The resulting behavior is ubiquitous and consistent (8,39). Investigators universally separate the response to local heat into two distinct phases (16,26).Investigators believe that these two phases are controlled by two mechanisms (26). When a local anesthetic is used to block sensory input, the first phase of the biphasic flow response is abolished, suggesting sensory neural-mediated microvascular dilation. The second phase is diminished with the addition of nitric oxide (NO) synthase (NOS) inhibitors (8,16,26), suggesting NO-dependent microvascular dilation. A direct link between the mechanisms of the neural-and NO-mediated increases in...

Skin blood flow increases in response to local heat due to sensorineural and nitric oxide (NO)-mediated dilation. It has been previously demonstrated that arteriolar dilation is inhibited with NO synthase (NOS) blockade. Flow, nonetheless, increases with local heat. This implies that the previously unexamined nonarteriolar responses play a significant role in modulating flow. We thus hypothesized that local heating induces capillary recruitment. We heated a portion (3 cm2) of the Pallid bat wing from 25 degrees C to 37 degrees C for 20 min, and measured changes in terminal feed arteriole (approximately 25 microm) diameter and blood velocity to calculate blood flow (n = 8). Arteriolar dilation was reduced with NOS and sensorineural blockade using a 1% (wt/vol) NG-nitro-L-arginine methyl ester (L-NAME) and 2% (wt/vol) lidocaine solution (n = 8). We also measured changes in the number of perfused capillaries, and the time precapillary sphincters were open with (n = 8) and without (n = 8) NOS plus sensorineural blockade. With heat, the total number of perfused capillaries increased 92.7 +/- 17.9% (P = 0.011), and a similar increase occurred despite NOS plus sensorineural blockade 114.4 +/- 30.0% (P = 0.014). Blockade eliminated arteriolar dilation (-4.5 +/- 2.1%). With heat, the percent time precapillary sphincters remained open increased 32.3 +/- 6.0% (P = 0.0006), and this increase occurred despite NOS plus sensorineural blockade (34.1 +/- 5.8%, P = 0.0004). With heat, arteriolar blood flow increased (187.2 +/- 28.5%, P = 0.00003), which was significantly attenuated with NOS plus sensorineural blockade (88.6 +/- 37.2%, P = 0.04). Thus, capillary recruitment is a fundamental microvascular response to local heat, independent of arteriolar dilation and the well-documented sensorineural and NOS mechanisms mediating the response to local heat.

Objective-Although it is well-established that the application of local heat causes a biphasic increase in skin blood flow, the responsible microvessels have not been identified.Methods-A bifurcating network of arterioles (1 st -5 th orders, 60-15 μm, n=10 per group) of the intact, unanesthetized, translucent bat wing were visualized on a transparent heat plate via intravital microscopy. Similar to previous bat wing studies, plate temperature was set at 25°C for 10 min then increased to 37°C for 20 min. Vessel diameter and red blood cell velocity were recorded and used to calculate resistance and blood flow.Results-The average flow response in arterioles was biphasic (p=0.02) and proportional to the temporal decrease in total resistance calculated from 1 st -5 th order arterioles. Metarteriole (i.e., 5 th order arteriole) resistance had the greatest impact on total resistance (-67.0±20.7%), and exhibited a biphasic trend that was opposed by temporal changes in resistance of 1 st -4 th order arterioles. Conclusion-Metarteriolesare not only necessary, but sufficient to explain the origin of the biphasic flow response in skin blood flow.

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