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 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).


CONCLUSIONS
Our study supports the view that RP/SSc is the result of defects in the peripheral vasculature.
Furspan
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PB
Department of Psychiatry, Internal Medicine, Wayne State University Detroit, Michigan 48201, USA. aa1985@wayne.edu
Mayes
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MD
Freedman
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RR
D000328:Adult; D001831:Body Temperature; D003000:Clonidine / Q000008:administration & dosage; D003080:Cold Temperature; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage; D019833:Genistein / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011928:Raynaud Disease / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage; D012867:Skin / Q000098:blood supply; D013565:Sympatholytics / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014699:Venules / Q000187:drug effects* / Q000201:enzymology*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D013565:Sympatholytics; D012701:Serotonin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D003000:Clonidine