iNOS-Dependent Cardioprotection by Cilostazol in Ischemia-Reperfusion Injury: Evidence from Isolated Rat Heart Model
Year: 2026
Type: article
Abstract: Myocardial Ischemia-Reperfusion (I/R) injury remains a major clinical challenge, and pharmacological strategies that mimic Ischemic Preconditioning (IPC) are of significant therapeutic interest. This study explored the cardioprotective potential of cilostazol and examined whether its effects are mediated through Inducible Nitric Oxide synthase (iNOS) derived from Nitrous Oxide (NO) signalling. Isolated rat hearts were subjected to 20 min of global ischemia followed by 40 mins of reperfusion using the Langendorff perfusion model. Animals were divided into six groups: Control (I/R), IPC (4 cycles of 5-min ischemia/reperfusion), and Cilostazol (50 μmol/L), Cilostazol + L-NAME (30 μmol/L; selective iNOS inhibitor). Cilostazol markedly reduced infarct size (21.167± 1.352%), comparable to IPC (20.167±0.792%) relative to the control group (66.667±2.539%). There were notable reductions in cardiac injury biomarkers, such as LDH (34.167±1.352 U/L) and CK-MB (1.667±0.494 U/L), reflecting the protective effects mediated by IPC. However, when L-NAME or aminoguanidine was administered alongside cilostazol, its protective effects were entirely nullified, causing the infarct size and biomarker levels to revert to those seen in untreated I/R hearts. Major Findings: Cilostazol’s cardioprotection is mediated primarily via iNOS/NO pathways, as evidenced by reversal with NOS inhibitors. Its efficacy parallels IPC, suggesting cilostazol as a non-invasive alternative to surgical preconditioning in procedures like Coronary Artery Bypass Grafting (CABG), enhancing patient compliance.
Source: Toxicology International
Authors: Junaid Tantray, Ashish Kumar Sharma
Institution: NIMS University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7148959778