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Title: An investigation into the pathogenesis of Raynaud's disease : the role of the vascular endothelium
Author: Smith, Paula J. W.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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The aim of this thesis was to investigate the role of the vascular endothelium in the development of cold-induced vasoconstriction, and in the pathophysiology of vasospasm in RD. Experiments were performed on resistance arteries in vitro and in vivo. The small vessel arteriograph (perfusion myograph) was used to study isolated arteries in vitro. Studies in vivo used the autoperfused hindlimb of the anaesthetised rat, in which stepped-cooling of the blood entering the hindlimb produced a rise in hindlimb perfusion pressure. Possible mediators of this cold-induced vasoconstriction were identified using antagonists selective for α-adrenoceptors and ET-receptors. Inhibitors of NO-synthase and cyclooxygenase were also examined. The α12-adrenoceptor antagonist, phentolamine, attenuated the cold-induced vasoconstriction, and was the only agent to have an effect that was significant in this model. The results demonstrate that the endothelium is an important modulator of cold-induced effects on the response to several vasoconstrictor agents, either by enhancing contraction through the release of vasoconstrictors such as ET, or by depressing contraction through the release of dilators, such as NO or PGI2. The effects of cooling on the responsiveness of an artery appears to depend on the type of vessel under study (cutaneous versus non-cutaneous). The results from the gluteal biopsy studies imply that the altered sensitivity to ET-1 at 37oC in RD patients is dependent on changes in dilator function, and not to altered sensitivity of the vascular smooth muscle to ET-1. Although an increase in the response to ET-1 was not found at 24oC, the results obtained at 37OC would support the hypothesis that the release and/or actions of NO is reduced in RD, allowing enhanced constriction of ET. These results suggest that the vascular endothelium is involved in the pathophysiology of RD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available