Nicorandil ameliorates cardiac microcirculation in hypertensive myocardial infarction via LKB1/AMPK signaling activation

Background: Hypertension is one of the most common chronic diseases in the world, affecting about a quarter of the adult population. Its complication, hypertensive myocardial infarction (HMI), has a complex pathological mechanism, involving myocardial ischemia, oxidative stress and microcirculation dysfunction. Objective: This study investigated the cardioprotective mechanisms of nicorandil (Nic), particularly its effects on cardiac microcirculation through modulation of the Liver Kinase B1 (LKB1)/AMP-activated Protein Kinase (AMPK) signaling pathway in HMI rats. Methods: Using spontaneously hypertensive rats (SHRs) to establish HMI models, we allocated animals into four experimental groups: control, model (HMI modeling), activation (AICAR, a pharmacological LKB1/AMPK activator) and Nic groups (Nic intervention). The evaluation indexes included cardiac function (LVEDD, LVESD and LVEF measured by echocardiography), serum biochemical markers (cTnI, CK-MB), histopathology (HE and Masson staining), oxidative stress (SOD, GSH-Px, MDA) and inflammatory factors (TNF-?, IL-6, IL-1?). The protein expression of LKB1/AMPK was analyzed by Western blot. Results: Compared with the control group, the model group exhibited significant suppression of LKB1/AMPK pathway activity, accompanied by marked myocardial fibrosis, elevated inflammatory cytokines and impaired cardiac function as evidenced by decreased Left Ventricular Ejection Fraction (LVEF) and increased Left Ventricular End-Systolic Diameter (LVESD) (P<0.05). Both pharmacological activation with AICAR and Nic treatment effectively restored LKB1/AMPK signaling, attenuated myocardial damage and significantly lowered oxidative stress and inflammatory markers (P<0.05 versus model group). Importantly, Nic treatment demonstrated superior efficacy compared to AICAR intervention in ameliorating HMI-induced pathological changes. Conclusion: Nic exerts cardioprotective effects in HMI rats through multi-target mechanisms involving LKB1/AMPK pathway activation, which subsequently attenuates oxidative stress and inflammatory responses while facilitating microcirculatory reconstruction, ultimately leading to significant improvement in cardiac function.