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Title: Purinergic signalling in chronic venous insufficiency and penile erection
Author: Metcalfe, Matthew James
ISNI:       0000 0004 2670 5084
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2006
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Chronic venous insufficiency (CVI) describes diseases of the lower limb veins in which venous return is impaired and varicose veins and skin ulceration may develop. The roles of purinergic signalling in regulation of vascular tone in the long saphenous vein (LSV) and in the trophic changes occurring in LSV muscle cells and epidermal keratinocytes in lower leg skin were studied. The purinergic role in penile blood flow was also studied, where regulation of penile blood flow affects tumescence. Purinergic signalling was studied using immunohistochemistry, organ bath pharmacology and electron microscopy. P2Xj, P2Yi, P2Y2, P2Y4 and P2Y6 receptor immunoreactivity was present on LSV smooth muscle. Purine-mediated muscle contractions were weaker in varicose veins. Electron microscopy and immunohistochemistry findings support the view that smooth muscle cells change from the contractile to the synthetic phenotype in varicose veins, associated with an upregulation of P2Yi and P2Y2 receptors and a down regulation of P2Xi receptors. CVI skin showed a decrease in P2X7 receptor expression and an increase in P2Yj, P2Y2 and P2X5 receptor expression in different epidermal layers. Mean skin epidermal area in CVI was reduced. Immunohistochemistry and RT-PCR techniques were used to study the presence of P2Y6 receptors in corpus cavernosal tissue. Using organ bath pharmacology, P2Y6 receptors on cavernosal tissue mediated relaxation which was diminished by a P2Y6 antagonist. In conclusion it is suggested that the LSV muscle cell phenotype change may be a causal factor in the development of varicose veins. The thinner epidermis found in CVI might be the result of the changes in expression of P2Y and P2X receptors on keratinocytes. Increased keratinocyte P2X5 receptor activity may, in part, be accountable for epidermal thinning in CVI. Purinergic modulation of human cavernosal smooth muscle cells via the P2Y6 receptor subtype might play a physiological role in penile erection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available