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-α, IL-6, IL-1β). 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.