Effect of temperature and modulators of protein tyrosine kinase activity on the reactivity of isolated venules in secondary Raynaud's phenomenon
Furspan, P.B.; Mayes, M.D.; Freedman, R.R.
Journal of Rheumatology 28(10): 2263-2268
2001
ISSN/ISBN: 0315-162X PMID: 11669167 Document Number: 527156
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 mum outside diameter) from normal (n=10) and RP/SSc (n=8) subjects to cooling and to contractile agents at 37 and 31degreeC. Results: The response to clonidine at 37degreeC 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 31degreeC, 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 muM). Venules from controls and patients with RP/SSc exhibited slight vasodilation to cooling from 37 to 31degreeC. In the presence of the protein tyrosine phosphatase inhibitor sodium orthovanadate (10 muM), 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.