Local warming of skin induces vasodilation by unknown mechanisms. To test whether nitric oxide (NO) is involved, we examined effects of NO synthase (NOS) inhibition with NG-nitro-L-arginine methyl ester (L-NAME) on vasodilation induced by local warming of skin in six subjects. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for delivery of L-NAME and sodium nitroprusside. Skin blood flow was monitored by laser-Doppler flowmetry (LDF) at microdialysis sites. Local temperature (Tloc) of the skin at both sites was controlled with special LDF probe holders. Mean arterial pressure (MAP; Finapres) was measured and cutaneous vascular conductance calculated (CVC = LDF/MAP = mV/mmHg). Data collection began with a control period (Tloc at both sites = 34 degrees C). One site was then warmed to 41 degrees C while the second was maintained at 34 degrees C. Local warming increased CVC from 1.44 +/- 0.41 to 4.28 +/- 0.60 mV/mmHg (P < 0.05). Subsequent L-NAME administration reduced CVC to 2.28 +/- 0.47 mV/mmHg (P < 0.05 vs. heating), despite the continued elevation of Tloc. At a Tloc of 34 degrees C, L-NAME reduced CVC from 1.17 +/- 0.23 to 0.75 +/- 0.11 mV/mmHg (P < 0.05). Administration of sodium nitroprusside increased CVC to levels no different from those induced by local warming. Thus NOS inhibition attenuated, and sodium nitroprusside restored, the cutaneous vasodilation induced by elevation of Tloc; therefore, the mechanism of cutaneous vasodilation by local warming requires NOS generation of NO.

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Surface roughness has been shown to affect differentiation and local factor production of MG63 osteoblast-like cells. This study examined whether surface roughness alters cellular response to circulating hormones such as 1 alpha,25-(OH)2D3. Unalloyed titanium (Ti) disks were pretreated with HF/HNO3 (PT) and then were machined and acid-etched (MA). Ti disks also were sandblasted (SB), sandblasted and acid etched (CA), or plasma sprayed with Ti particles (PS). The surfaces, from smoothest to roughest, were: PT, MA, CA, SB, and PS. MG63 cells were cultured to confluence on standard tissue culture polystyrene (plastic) or the Ti surfaces and then treated for 24 h with either 10(-8) M or 10(-7) M 1 alpha,25-(OH)2D3 or vehicle (control). Cellular response was measured by assaying cell number, cell layer alkaline phosphatase specific-activity, and the production of osteocalcin, latent (L) TGF beta, and PGE2. Alkaline phosphatase activity was affected by surface roughness; as the surface became rougher, the cells showed a significant increase in alkaline phosphatase activity. Addition of 1 alpha,25-(OH)2D3 to the cultures caused a dose-dependent stimulation of alkaline phosphatase activity that was synergistic with the effect caused by surface roughness alone. 1 alpha,25-(OH)2D3 also caused a synergistic increase in osteocalcin production as well as local factor (LTGF beta and PGE2) production on the rougher CA, SB, and PS surfaces, but it had no effect on the production on smooth surfaces. The inhibitory effect of surface roughness on cell number was not affected by 1 alpha,25-(OH)2D3 except on the SB surface. 1 alpha,25-(OH)2D3 decreased cell number, increased alkaline phosphatase activity and osteocalcin production, and had no effect on LTGF beta or PGE2 production by MG63 cells grown on tissue culture polystyrene. These data suggest that bone cell response to systemic hormones is modified by surface roughness and that surface roughness increases the responsiveness of MG63 cells to 1 alpha,25-(OH)2D3. They also suggest that the endocrine system is actively involved in normal bone healing around implants.

Whether nitric oxide (NO) is involved in cutaneous active vasodilation during hyperthermia in humans is unclear. We tested for a role of NO in this process during heat stress (water-perfused suits) in seven healthy subjects. Two forearm sites were instrumented with intradermal microdialysis probes. One site was perfused with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) dissolved in Ringer solution to abolish NO production. The other site was perfused with Ringer solution only. At those sites, skin blood flow (laser-Doppler flowmetry) and sweat rate were simultaneously and continuously monitored. Cutaneous vascular conductance, calculated from laser-Doppler flowmetry and mean arterial pressure, was normalized to maximal levels as achieved by perfusion with the NO donor nitroprusside through the microdialysis probes. Under normothermic conditions, L-NAME did not significantly reduce cutaneous vascular conductance. During hyperthermia, with skin temperature held at 38-38.5 degreesC, internal temperature rose from 36.66 +/- 0.10 to 37.34 +/- 0.06 degreesC (P < 0.01). Cutaneous vascular conductance at untreated sites increased from 12 +/- 2 to 44 +/- 5% of maximum, but only rose from 13 +/- 2 to 30 +/- 5% of maximum at L-NAME-treated sites (P < 0.05 between sites) during heat stress. L-NAME had no effect on sweat rate (P > 0.05). Thus cutaneous active vasodilation requires functional NO synthase to achieve full expression.

EMD affects early states of osteoblastic maturation by stimulating proliferation, but as cells mature in the lineage, EMD enhances differentiation.