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Title: Pulmonary vascular reactivity and fluid balance
Author: Mundy, Alexa Lee
ISNI:       0000 0001 3431 3943
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2000
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This thesis is concerned with pulmonary vascular responses to hypoxia and with pulmonary fluid balance in the rabbit. The isolated perfused lung was used to investigate these issues; dextran and albumin (in varying concentrations) were added to the perfusate as colloids. Albumin was found to be more effective at delaying pulmonary oedema than dextran, probably due to its molecular shape and charge. Having established an effective preparation, the effects of hypoxia were studied. Hypoxia elicited a rapid increase in pulmonary vascular resistance (PVR), followed by a decline to a plateau above the euoxic baseline over two hours. Multiple exposures to hypoxia resulted in an attenuation of the initial vasoconstriction with a potentiation of the slower vasoconstriction. Endothelin-1 (ET-1) is a potent vasoconstrictor, which has been suggested to play a role in hypoxic pulmonary vasoconstriction (HPV). Phosphoramidon (an inhibitor ET-1 production and degradation) enhanced both phases of HPV, indicating that ET-1 does not mediate HPV, although it plays a modulatory role. The inhibition of nitric oxide synthase (NOS) by N°-nitro-L-arginine methyl ester (L-NAME) reduced both phases of HPV; this may have been due to L-NAME's antagonism of muscarinic receptors. L-NAME also caused an increase in the rate of weight gain of the isolated lung. This increase was attenuated by a mast cell stabilizer (lodoxamide) as well as by a cGMP analog (8Br-cGMP), indicating that nitric oxide may usually aid pulmonary fluid balance by stabilizing mast cells and by relaxing endothelial cells via cGMP. The role of the ET B receptor in HPV was studied in isolated rabbit pulmonary arteries mounted on a tension myograph. Hypoxia elicited a small initial vasoconstriction followed by a large dilation, which slowly lessened over two hours. The initial vasoconstriction was found to be endothelium-dependent, while the subsequent vasodilation was endothelium-independent. Antagonism of the ET B receptor with BQ- 788 slightly potentiated the initial vasoconstriction to hypoxia, while the subsequent dilation remained unchanged. The ET B receptor was not found to have a great influence on HPV in this preparation.
Supervisor: Dorrington, Keith L. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Rabbits as laboratory animals ; Lungs ; Blood-vessels