Abstract
OBJECTIVE: To investigate the response of skin venules from healthy controls and scleroderma patients with Raynaud's phenomenon (RP/SSc) to cooling and to modulators of protein tyrosine kinase (PTK) activity at normal and reduced temperature. METHODS: We used the microvessel perfusion technique to characterize the response of isolated dermal venules (200-400 microm outside diameter) from normal (n = 10) and RP/SSc (n = 8) subjects to cooling and to contractile agents at 37 and 31 degrees C. RESULTS. The response to clonidine at 37 degrees C was less in venules from patients with RP/SSc compared to controls; the contraction to serotonin was greater in venules from RP/SSc patients versus controls; at 31 degrees C, venules from RP/SSc patients contracted to both clonidine and serotonin to a greater extent versus controls; and contraction to these agonists was reversed by cumulative addition of genistein (1-100 microM). Venules from controls and patients with RP/SSc exhibited slight vasodilation to cooling from 37 to 31 degrees C. In the presence of the protein tyrosine phosphatase inhibitor sodium orthovanadate (10 microM), venules from controls now exhibited a small contraction (-5.1 +/- 3.2%) and venules from RP/SSC subjects a significantly greater contraction (-38.7 +/- 9.0%; p < 0.05). CONCLUSION: Our study supports the view that RP/SSc is the result of defects in the peripheral vasculature.