Functional alterations in NO, PGI₂ and EDHF pathways in the aortic endothelium after myocardial infarction in rats

Background: Previous work on endothelial dysfunction in post-MI heart failure has shown conflicting results. Aim: To analyze gender related alterations in NO-, PGI₂- and EDHF-dependent endothelial function in the thoracic aorta 7 and 42 days after myocardial infarction (MI). Methods and results: MI was induced by coronary artery ligation in female and male Sprague-Dawley rats. There was no gender related difference in infarct-size or in the impairment of fractional shortening of the left ventricle 42 days after coronary ligation. Neither acetylcholine-induced (Ach) vasodilation nor basal PGI₂ production in the aorta was modified by coronary ligation. Interestingly, 7 days after MI, basal NO production was impaired and the EDHF component of Ach-induced vasodilation was up-regulated, in both male and female rats. However, 42 days post-MI, basal NO was only impaired in male rats, while EDHF was only up-regulated in female rats. Conclusion: MI induced impairment of functional activity of basal NO production and adaptive up-regulation of the EDHF component of Ach-induced relaxation. The above alterations in endothelial function in the aorta were gender-specific at 42 days but not 7 days after MI. Some of the previously reported discrepancies in the development of endothelial dysfunction in the post-MI period may be gender related differences.