P301	Distribution and vasodilatory function of nitric oxide and superoxide after myocardial infarction.
1A.Berges, 2L.Van Nassauw, 2J-P.Timmermans, 1Chr.Vrints
1University of Antwerp - Cardiology, Antwerp, BE; 2University of Antwerp - Cell biology and Histology, Antwerp, BE.

We previously showed that permanent ischaemia leads to endothelial dysfunction in non-infarcted coronary arteries, which could be related to enhanced NOS activation. This study aimed to clarify the functional role and time-dependent induction of NO and superoxide during postinfarction remodelling. The rat coronary ligation model was used to induce an anterior infarction. One day, one week or three weeks after surgery, immunohistochemical analyses of iNOS, eNOS, NADH oxidase and peroxynitrite were performed. Moreover, samples were taken to analyse the levels of serum nitrite and superoxide production. The mRNA amount of iNOS, eNOS and NADH oxidase was determined using real-time RT-PCR. In addition, participation of total NO, iNOS-derived NO and oxidative stress in vasodilator responses was examined in a Langendorff setup. NO-mediated vasodilatation was significantly increased one week after ischaemia, but normalised later on. This was confirmed by a transient increase in the serum nitrite level. Ischaemia led to a modest but constant activation of eNOS, while iNOS showed a drastic but transient de novo formation. However, no influence of iNOS-derived NO on coronary vasodilatation could be detected. Indeed, eNOS was mostly observed in blood vessels throughout the entire myocardium, whereas iNOS was found in macrophages and myocytes of the non-infarcted ventricle. In addition, a progressively increased production of superoxide was detected during remodelling. While there was an acute activation of NADH oxidase in blood vessels and macrophages, we observed a large and time-dependent de novo synthesis in cardiomyocytes. Moreover, a large formation of peroxynitrite was found after ischaemia. However, continuous perfusion with superoxide scavenger or NADH oxidase antagonist had no effect on coronary flow responses. In conclusion, postinfarction remodelling increases activation of NOS. eNOS-derived NO modulates coronary adaptations after ischaemia, while iNOS-derived NO regulates anatomic modifications, such as scar formation, myocardial hypertrophy and ventricle dilatation. However, the additional increased production of superoxide reduces the bio-availability and beneficial effects of NO, leading to further deterioration of endothelial and inotropic function. Supported by FWO grant G.0422.02.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.