Increment in nNOS and Akt‐eNOS pathway in coronary arteries post‐myocardial infarction can prevent the onset of heart failure

The imbalance in NO modulation in coronary artery (CA) has been observed in cardiovascular diseases. We tested the hypothesis that NO modulation in CA could be differently adjusted after myocardial infarction (MI) in the presence or absence of heart failure (HF). Male Wistar rats were submitted to CA ligation (MI) or sham operation (SHAM). After 4 weeks, the infarcted rats were divided in two groups: without (INF) or with HF according to hemodynamic parameters and the septal CA was mounted in a wire myograph. The acetylcholine (ACh, 100ñM‐100μM)‐induced relaxation was decreased (35%) in HF, while it was enhanced (61%) in INF CA. The ACh‐induced NO production evaluated by 4,5‐diaminofluorescein diacetate was reduced in CA of HF, while it was increased in INF. The NO synthase (NOS) (L‐NAME, 100μM), neuronal (n) NOS (7‐NI, 100μM) and PI3‐kinase (LY294002, 50μM) inhibitors abolished the enhanced ACh‐induced relaxation observed in CA of INF. In addition, endothelial (e) and nNOS isoforms and Akt protein expression were greater in CA of INF than SHAM. The endothelium‐independent relaxation was similar among groups. CA from MI showed increased NO modulation due to nNOS and Akt‐eNOS pathway, although CA from HF presents endothelial dysfunction. These results support the idea that NO can prevent the onset of HF after MI. Supported: FAPESP/CNPq.