Pak J Pharm Sci. 2026 Mar;39(3):604-611. doi: 10.36721/PJPS.2026.39.3.REG.14441.1.
ABSTRACT
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.
PMID:41620890 | DOI:10.36721/PJPS.2026.39.3.REG.14441.1