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Studies on the release of endogenous renal dopamine and assessment of the renal dopamine prodrug gludopa in normal man

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JeffreyRF_1989redux.pdf (31.71Mb)
Date
1989
Author
Jeffrey, Robin Fraser
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Abstract
 
 
The diverse experimental approaches into the actions of dopamine in the periphery have demonstrated the amine to possess various interesting features. By activation of distinct receptors it is capable of producing systemic and renal vasodilatation and of modulating sympatho-adrenal outflow. By a combination of haemodynamic and direct tubular effects it is actively natriuretic, and influences hormonal release from the kidney and adrenal cortex.
 
A physiological function in the kidney is strongly suggested by the prod¬ uction and excretion of large amounts of free dopamine, by the close relation¬ ship between dopamine excretion and sodium output in the urine, and by the characterisation of a widespread distribution of dopamine receptors. Such observations do not however, prove that endogenous dopamine has physiological So 3 significance and more compelling evidence accrues when an inhibitor of dopamine can be shown to alter some parameter of normal function. Such studies have been approached using either dopamine receptor antagonists or dopa decarboxylase inhibitors to block dopamine synthesis, and a number of animal models have been utilised, notably in man, dog and rat.
 
It can be concluded for the present studies and from other reported work that dopamine exerts independent action in the kidney, without the requisite mediation of other hormonal, neural or physical factors. More likely is a system of parallel influences, including dopamine, interacting in an array of negative and positive feedback loops, forming a highly complex control mechanism which maintains homeostasis and is able to respond rapidly to changes in the local and wider environment.
 
URI
http://hdl.handle.net/1842/26645
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  • Edinburgh Medical School thesis and dissertation collection

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