Functional studies in small arteries do not support a primary role for endothelin in the pathogenesis of Raynaud's disease.
Endothelin-1 (ET-1) has been implicated in the pathogenesis of Raynaud's disease (RD). This study examined the effect of cooling on the response to ET-1 in human microvessels. Subcutaneous small arteries were dissected from gluteal fat biopsies taken from patients with RD (n = 20) and from age- and sex-matched control subjects (n = 17) and were cannulated in a small vessel arteriograph. Cumulative concentration-response curves to ET-1 (10(-12) to 3 x 10(-7) M) were obtained in vessels at 37 degrees C and 24 degrees C, with the endothelium either intact or removed (n = 6 per group). There were no significant differences in responses to ET-1 between RD patients and controls in either intact or denuded vessels, at either 37 degrees C or at 24 degrees C. There was, however, a significant endothelium-dependent interaction between the groups when the effect of temperature on the response to ET-1 was examined (p = 0.01; two-way ANOVA). Whereas cooling tended to reduce the sensitivity in RD, the opposite effect was observed in controls. Measurements of plasma ET-1 did not reveal any significant difference between patients with RD and healthy controls. These results suggest that ET-1 does not play a primary pathophysiologic role in RD. ET-1 might be responsible for mediating the prolonged vasospasm in RD, but secondary to another factor(s), such as impaired endothelium-dependent vasodilation.
Smith
P J
PJ
Department of Medicine, Western General Hospital, University of Edinburgh, Scotland.
Ferro
C J
CJ
McQueen
D S
DS
Webb
D J
DJ
D000328:Adult; D001158:Arteries / Q000503:physiopathology*; D001831:Body Temperature / Q000502:physiology; D019332:Endothelin-1 / Q000096:biosynthesis; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011928:Raynaud Disease / Q000473:pathology / Q000503:physiopathology*; D012867:Skin / Q000473:pathology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D016232:Endothelins