Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.657790
Title: Investigation of inducible nitric oxide synthase in an experimental model of chronic heart failure
Author: Miller, A. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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Abstract:
Impaired nitric oxide (NO)-mediated vasodilatation has been implicated in the increased peripheral vascular resistance (PVR) associated with chronic heart failure (CHF). However, there is evidence that basal synthesis of NO may be preserved or even enhanced in CHF, perhaps due to the expression of the inducible NO synthase (iNOS). Increased superoxide production has been demonstrated in CHF and, some superoxide destroys NO, a reduction in NO bioavailability may be responsible for impaired NO-mediated relaxations and may also explain why PVR remains elevated despite increased NO production. Therefore, the aims of this thesis were to investigate the expression of iNOS in the cardiovascular system of rats with CHF following coronary artery ligation, to determine the functional significance of this potential source of NO on responsiveness of the peripheral vasculature, and to investigate the role that superoxide plays in modulating vascular function. Immunohistochemical studies revealed that iNOS was expressed in all cell types of small mesenteric arteries and in thoracic aortae from CHF rats. iNOS was also identified in coronary vascular, endocardial and myo-endothelial cells in hearts from CHF rats. Immunoreactive iNOS was also found throughout the viable left ventricle of hearts for CHF rats. No staining was found in arteries or hearts from sham-operated rats. The salient finding of this thesis is that iNOS is expressed in the peripheral vasculature and in the heart in this model of CHF. However, in small mesenteric arteries, which play a pivotal role in determining PVR, substrate deficient iNOS-derived superoxide is responsible for increased responsiveness to constriction agents. In thoracic aortae, however, iNOS appears to play no role in modulating vascular function. In conclusion, the findings of this thesis may represent an important mechanism for the raised PVR and endothelial dysfunction associated with CHF.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.657790  DOI: Not available
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