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Title: The impact of hepatic cirrhosis on the contractile function of human hepatic arteries
Author: Islam, Md Zahurul
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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The aims of this thesis was (i) to assess the effect of cirrhosis on the responses of human hepatic artery to three vasoconstrictor agonists, arginine vasopressin (AVP), 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1), which may contribute to the development of the hyperdynamic circulation and (ii) to clarify the mechanism(s) of any abnormally detected. The endothelium was shown to be damaged considerably in isolated human and porcine hepatic arteries, hence, all subsequent studies used denuded vessels. The protocol developed using porcine hepatic arteries demonstrated that preservative solutions had no effect on contractile function but did alter endothelium-independent relaxation. Responses to vasoconstrictors were altered in arteries from patients with hepatic cirrhosis although the nature of this alteration was agonist-dependent: the maximum contraction to AVP was impaired whilst that to 5-HT was augmented. In contrast, the sensitivity of response to ET-1 was increased, whereas KCl-mediated contraction was unchanged. The contractile responses to AVP, 5-HT and KCl were unaffected by NOS inhibition. There was no immunoreactivity for iNOS in donor hepatic arteries nor in those from most patients: low level of iNOS were only detected in arteries from patients with alcoholic liver disease. Use of antagonists demonstrated that AVP and ET-1 contracted human hepatic arteries via the V1 and ETA receptors, respectively, whilst 5-HT acted predominantly via 5-HT1-like receptors with a small contribution from the 5-HT2A subtype. These studies demonstrated that cirrhosis of the liver is associated with a agonist-selective alteration of receptor-mediated contraction in denuded human hepatic arteries. Inducible nitric oxide synthase activity did not contribute to these alterations and unaltered responses to KCl suggest that these abnormalities are not due to structural changes in the vessel wall. These results indicate, therefore, that altered contractile function in hepatic arteries from patients with cirrhosis are due to changes in receptor activity and/or post-receptor signal transduction pathways.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available