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Role of Nitric Oxide in Posthypoxic Contractile Dysfunction of Diabetic Cardiomyopathy


El-Omar, MM and Lord, RJ and Draper, NJ and Shah, AM, Role of Nitric Oxide in Posthypoxic Contractile Dysfunction of Diabetic Cardiomyopathy, The European Journal of Heart Failure, 5, (3) pp. 229-239. ISSN 1388-9842 (2003) [Refereed Article]

DOI: doi:10.1016/S1388-9842(03)00010-2


We investigated the role of nitric oxide synthase (NOS) in the contractile dysfunction of diabetic cardiomyopathy, comparing streptozotocin-treated (60 mg/kg) diabetic Wistar rats with matched non-diabetic controls. Isolated isovolumic heart function was studied during normoxia and in response to brief hypoxia-reoxygenation. Diabetic hearts had significantly lower left-ventricular pressure and slower isovolumic relaxation than controls (relaxation time constant, T 40.2 ± 2.3 vs. 27.7 ± 0.9 ms; P <0.05) and a blunted response to hypoxia. These abnormalities were unaffected by NOS inhibition. Upon reoxygenation after brief hypoxia, diabetic hearts exhibited substantial worsening of LV relaxation compared to normal hearts (T 69.1 ± 3.3 vs. 56.6 ± 7.9 ms; P < 0.05). This post-hypoxic diastolic dysfunction was significantly attenuated either by the non-selective NOS inhibitor L-NAME, the iNOS inhibitor L-NIL, or the reactive-oxygen-species (ROS) scavenger thiourea. Only diabetic hearts expressed iNOS protein, whereas eNOS expression was similar in both groups. In conclusion, diabetic hearts exhibit markedly abnormal post-hypoxic relaxation, which is attributable to both ROS and NO derived from iNOS. © 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Surgery
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Lord, RJ (Dr Roger Lord)
ID Code:29090
Year Published:2003
Web of Science® Times Cited:20
Deposited By:Surgery
Deposited On:2003-08-01
Last Modified:2004-07-05

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