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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/H2152    most recent 00326.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Kim, S.-J. Articles by Hintze, T. H. Search for Related Content PubMed PubMed Citation Articles by Kim, S.-J. Articles by Hintze, T. H.

Evidence for enhanced eNOS function in coronary microvessels during the second window of protection

¹Section of Cardiology, Advocate Illinois Masonic Medical Center, and ²Department of Physiology and Biophysics, University of Illinois, Chicago, Illinois; ³Department of Physiology, New York Medical College, Valhalla, New York; ⁴Cardiovascular Research Institute and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey; and ⁵Department of Anesthesiology, Advocate Illinois Masonic Medical Center, and University of Illinois, Chicago, Illinois

Submitted 29 March 2006 ; accepted in final form 16 January 2007

Nitric oxide (NO) derived from endothelial NO synthase (NOS) (eNOS) has been identified as a trigger for the second window of protection (SWOP), but its role as a mediator during the SWOP is a matter of debate. Eighteen mongrel dogs were chronically instrumented to measure left ventricular function, coronary blood flow, and wall thickening. Myocardial preconditioning was induced by 10 min coronary artery occlusion. After 24 h of reperfusion (during the SWOP), the hearts were excised. Coronary microvessels were isolated and incubated in presence of 1) the endothelium-dependent agonists carbachol and bradykinin, 2) the calcium ionophore A23187 [GenBank] , and 3) the angiotensin-converting enzyme (ACE) inhibitors enalaprilat and ramiprilat. Nitrite, a metabolite of NO, was measured. Under baseline conditions, nitrite production in microvessels from SWOP was 30% higher than that from normal (96 ± 4 vs. 74 ± 3 pmol/mg, P < 0.01, respectively). Nitrite production in response to carbachol, bradykinin, and A23187 [GenBank] was also enhanced in microvessels from SWOP (P < 0.05). These enhanced responses were abolished by N^G-nitro-L-arginine methyl ester (L-NAME) or the endothelial receptor-specific antagonists atropine and HOE-140. The level of eNOS protein in the SWOP myocardium was twofold higher than that in the non-SWOP myocardium. Nitrite production in response to the ACE inhibitors was greater in microvessels from SWOP. These effects were blocked by L-NAME, HOE-140, or dichloroisocoumarin (which inhibits kinin formation). We found that a brief ischemic episode induced delayed, enhanced NO production in coronary microvessels and an upregulation of eNOS protein. These findings suggest that eNOS is a mediator during the SWOP. The ability of ACE inhibitors to enhance NO release during the SWOP points to an additional clinical application for these drugs.

ischemic preconditioning; coronary circulation; endothelium; nitric oxide; angiotensin-converting enzyme inhibitors