Studies into the role of endogenous angiotensin 11 in the regulation of peripheral vascular tone in health and disease
Studies into the role of endogenous angiotensin 11 in the regulation of peripheral vascular tone in health and disease
The purpose of the present series of studies was to determine the contribution of angiotensin II to basal and sympathetically stimulated peripheral vascular tone in healthy sodium replete and deplete volunteers, and in patients with liver cirrhosis and chronic heart failure.
In dorsal hand veins, losartan, a selective AT1 receptor antagonist, attenuated the venoconstriction induced by angiotensin II but had no effect on the responses to noradrenaline nor venoconstriction induced by a single deep breath.
In forearm resistance vessels of sodium replete healthy volunteers, intra-arterial losartan caused no significant changes in basal forearm blood flow, forearm vascular resistance or sympathetically stimulated forearm vasoconstriction. However, sodium depletion more than doubled plasma angiotensin II concentrations after which losartan increased forearm blood flow in a dose dependent manner. Patients with heart failure and those with cirrhosis demonstrated significant vasodilatation to losartan and had a significantly reduced lower body negative pressure response compared to controls. In contrast to patients with heart failure in which the response was normal, exogenous angiotensin II mediated vasoconstriction was attenuated in patients with cirrhotic liver disease. The forearm sympathetically mediated vasoconstrictor response to low pressure baroreceptor unloading was unaffected by AT1 receptor antagonism.
These studies indicate that angiotensin II does not contribute to basal forearm resistance vessel tone except under circumstances of renin-angiotensin system activation such as sodium depletion, chronic heart failure and cirrhotic liver disease. Despite normal responsiveness to noradrenaline, chronic heart failure and cirrhotic liver disease are associated with an impairment of reflexive forearm vasoconstriction produced by baroreceptor unloading. Moreover, acute AT1 antagonism does not appear to attenuate the sympathetically mediated peripheral vasoconstriction associated with low pressure baroreceptor unloading: a potentially important distinction from the sympatholytic actions of angiotensin converting enzyme inhibition.
University of Southampton
1999
Newby, David Ernest
(1999)
Studies into the role of endogenous angiotensin 11 in the regulation of peripheral vascular tone in health and disease.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The purpose of the present series of studies was to determine the contribution of angiotensin II to basal and sympathetically stimulated peripheral vascular tone in healthy sodium replete and deplete volunteers, and in patients with liver cirrhosis and chronic heart failure.
In dorsal hand veins, losartan, a selective AT1 receptor antagonist, attenuated the venoconstriction induced by angiotensin II but had no effect on the responses to noradrenaline nor venoconstriction induced by a single deep breath.
In forearm resistance vessels of sodium replete healthy volunteers, intra-arterial losartan caused no significant changes in basal forearm blood flow, forearm vascular resistance or sympathetically stimulated forearm vasoconstriction. However, sodium depletion more than doubled plasma angiotensin II concentrations after which losartan increased forearm blood flow in a dose dependent manner. Patients with heart failure and those with cirrhosis demonstrated significant vasodilatation to losartan and had a significantly reduced lower body negative pressure response compared to controls. In contrast to patients with heart failure in which the response was normal, exogenous angiotensin II mediated vasoconstriction was attenuated in patients with cirrhotic liver disease. The forearm sympathetically mediated vasoconstrictor response to low pressure baroreceptor unloading was unaffected by AT1 receptor antagonism.
These studies indicate that angiotensin II does not contribute to basal forearm resistance vessel tone except under circumstances of renin-angiotensin system activation such as sodium depletion, chronic heart failure and cirrhotic liver disease. Despite normal responsiveness to noradrenaline, chronic heart failure and cirrhotic liver disease are associated with an impairment of reflexive forearm vasoconstriction produced by baroreceptor unloading. Moreover, acute AT1 antagonism does not appear to attenuate the sympathetically mediated peripheral vasoconstriction associated with low pressure baroreceptor unloading: a potentially important distinction from the sympatholytic actions of angiotensin converting enzyme inhibition.
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Published date: 1999
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Local EPrints ID: 463959
URI: http://eprints.soton.ac.uk/id/eprint/463959
PURE UUID: f6c4147e-e154-457e-8cb0-aea9bb8ec574
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Date deposited: 04 Jul 2022 20:59
Last modified: 04 Jul 2022 20:59
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Author:
David Ernest Newby
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