Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.776189
Title: The influence of angiotensin II on airway function in asthma
Author: Millar, Evelyn A.
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1996
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Abstract:
The renin-angiotensin system (RAS) is an endocrine system principally involved in the maintenance of cardiovascular homeostasis and electrolyte balance, its actions being mediated by the octapeptide hormone angiotensin II (ANG II). In a preliminary observation we found marked activation of the RAS in acute severe asthma. The stimulus to this activation, and the possible consequences of elevated ANG II on lung function in man were unknown, although ANG II had recently been shown to potentiate bronchoconstriction of rabbit airway smooth muscle in vitro. The purpose of our investigation was to examine possible stimuli to ANG II release in acute asthma and also the direct and indirect effects of this hormone on airway function in vivo in man. Initial studies confirmed that single and multiple high doses of nebulised and also intravenous beta2 agonists used in the treatment of asthma eg salbutamol, elevate ANG II levels in the plasma, but the levels achieved were less than those observed in acute severe asthma. Further studies revealed that hypoxia did not cause activation of the RAS in normal volunteers, nor did it potentiate the effect of nebulised beta2 agonists. We also demonstrated that the elevation of ANG II levels by nebulised beta2 agonists can be prevented by pretreatment with ACE inhibitor drugs (lisinopril), suggesting that this action of beta2 agonists on the RAS is mediated via the classical components of the RAS, including ACE, rather than involving alternative pathways of ANG II generation. When administered by intravenous infusion to produce similar plasma levels to those observed in acute asthma, ANG II caused bronchoconstriction in mild asthmatic patients, and in lower (subthreshold) doses potentiated the effect of inhaled methacholine both in vitro in isolated human bronchi and also in vivo, in mild asthmatic patients. We therefore conclude from this series of experiments that the RAS is activated in acute severe asthma and that high dose beta2 agonists are likely to be partly responsible for this activation. The role of other possible stimuli, perhaps inflammatory mediators such as proteinase enzymes released from mast cells, remains to be established. Our findings also suggest a role for ANG II as a mediator in asthma, and further studies to examine the effects of ANG II receptor antagonists in different forms of experimental asthma are now indicated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.776189  DOI:
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