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Title: Vascular endothelin-1 production and receptor subtypes in chronic heart failure
Author: Mickley, Emma J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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The aims of this thesis were i). to characterise the ET receptors on the smooth muscle of normotensive rats, ii). investigate any changes of the ET receptor subtypes in a CHF rat model and in CHF patients and iii). investigate whether there is increased ET-1 synthesis in CHF by measuring plasma ET-1 and big ET-1 levels and if there is an altered localisation of ET-1 and ECE in the wall of the arteries. Firstly, the ET-1 receptor subtypes responsible for ET-1-induced vasoconstriction in endothelium-denuded mesenteric arteries from normotensive Wistar rats were investigated. Arteries were mounted in a perfusion myograph and ET-1 or sarafotoxin S6c (SRTX S6c) concentration-response curves (CRC) were performed. The relative roles of the ETA and ETB receptors in the ET-1 induced vasoconstrictions were evaluated by using either the ETA receptor antagonist, BQ-123; the ETB receptor antagonist, BQ-788; the ETB receptor agonist, SRTX S6c or the non-selective ETA/ETB antagonist, TAK-044. Both ETA and ETB receptors were found to mediate ET-1 vasoconstriction and that ETA receptors could compensate for the inhibition of ETB receptors. The results suggested a potential crosstalk mechanism between the two receptor subtypes. Any changes in vascular smooth muscle ET receptor responses and subtypes mediating ET-1 vasoconstriction in resistance arteries in CHF were then investigated. Two sources of arteries were used; i). mesenteric arteries from rats at two different time points after the induction of heart failure by left coronary artery ligation or sham-operation and ii). gluteal arteries dissected from buttock biopsies obtained from Grade II & III CHF patients and age-matched controls.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available