Journal
CARDIOVASCULAR RESEARCH
Volume 115, Issue 1, Pages 168-178Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvy157
Keywords
Vascular endothelial growth factor; Endothelial nitric oxide synthase; Cardiac Preconditioning; Ischaemia; reperfusion
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Funding
- National Institutes of Health from the United States Public Health Services, Bethesda, MD, USA [P01GM 066730]
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Aims Previous studies indicate that nitric oxide derived from endothelial nitric oxide synthase (eNOS) serves as both trigger and mediator in anaesthetic cardiac preconditioning. The mechanisms underlying regulation of eNOS by volatile anaesthetics have not been fully understood. Therefore, this study examined the role of vascular endothelial growth factor (VEGF) in isoflurane cardiac preconditioning. Methods and results Wistar rats underwent 30min of coronary artery occlusion followed by 2h of reperfusion. Isoflurane given prior to ischaemia/reperfusion significantly decreased myocardial infarct size from 601% in control to 40 +/- 3% (n=8 rats/group, P<0.05). The beneficial effects of isoflurane were blocked by neutralizing antibody against VEGF (nVEGF). Coronary arterial endothelial cells (ECs) alone or together with cardiomyocytes (CMs) were subjected to hypoxia/reoxygenation injury. The expression of VEGF and eNOS was analysed by western blot, and nitric oxide was measured by ozone-based chemiluminescence. In co-cultured CMs and ECs, isoflurane administered before hypoxia/reoxygenation attenuated lactate dehydrogenase activity and increased the ratio of phosphorylated eNOS/eNOS and nitric oxide production. The protective effect of isoflurane on CMs was compromised by nVEGF and after VEGF in ECs was inhibited with hypoxia inducible factor-1 short hairpin RNA (shRNA). The negative effect of hypoxia inducible factor-1 shRNA was restored by recombinant VEGF. Conclusion Isoflurane cardiac preconditioning is associated with VEGF regulation of phosphorylation of eNOS and nitric oxide production.
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