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Role of Nitric Oxide in Posthypoxic Contractile Dysfunction of Diabetic Cardiomyopathy
journal contribution
posted on 2023-05-16, 14:49 authored by El-Omar, MM, Lord, RJ, Draper, NJ, Shah, AMWe 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.
History
Publication title
The European Journal of Heart FailureVolume
5Pagination
229-239ISSN
1388-9842Department/School
Tasmanian School of MedicinePublisher
ElsevierPlace of publication
NetherlandsRepository Status
- Restricted