Effect of temperature and modulators of protein tyrosine kinase activity on the reactivity of isolated venules in secondary Raynaud's phenomenon

Objective. To investigate the response of skin venules from healthy control s and scleroderma patients with Raynaud's phenomenon (RP/SSc) to cooling an d to modulators of protein tyrosine kinase (PTK) activity at normal and red uced temperature. Methods. We used the microvessel perfusion technique to characterize the re sponse of isolated dermal venules (200-400 mum outside diameter) from norma l (n = 10) and RP/SSc (n = 8) subjects to cooling and to contractile agents at 37 and 31 degreesC. Results. The response to clonidine at 37 degreesC 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 degreesC, ve nules from RP/SSc patients contracted to both clonidine and serotonin to a greater extent versus controls; and contraction to these agonists was rever sed by cumulative addition of genistein (1-100 muM). Venules from controls and patients with RP/SSc exhibited slight vasodilation to cooling from 37 t o 31 degreesC. In the presence of the protein tyrosine phosphatase inhibito r sodium orthovanadate (10 muM), venules from controls now exhibited a smal l contraction (-5.1 +/- 3.2%) and venules from RP/SSC subjects a significan tly greater contraction (-38.7 +/- 9.0%; p < 0.05). Conclusion. Our study supports the view that RP/SSc is the result of defect s in the peripheral vasculature.