Vitamin B6 (pyridoxine) vitamins are of interest in preventative and protective strategies in cardiovascular disease. However, the safety and efficacy of vitamin B6 has been questioned. The aim of this study was to study the protective effect of pyridoxine, amlodipine, and their combination against vasopressin-induced angina model in rats. The administration of vasopressin (1 IU/kg, i.v.) to the rats elevated the S-wave level of the electrocardiogram reflecting the presence of subendocardial ischemia, whereas it decreased of the heart rate, resulting in the increase of the cardiac enzymes, creatine kinase MB (CK MB), and lactate dehydrogenase (LDH). In the vasopressin-induced angina model, oral administration of pyridoxine in dose of 5, 7, 10 mg/kg revealed dose-dependent suppression of vasopressin-triggered of ST elevation and in reduced of heart rat. In addition, pyridoxine produced dose-dependent suppression of cardiac enzymes, creatine kinase MB (CK MB), and lactate dehydrogenase (LDH) more than amlodipine and isosorbide; while in contrast, the combination of pyridoxine with amlodipine resulted in a trend towards increased adverse cardiovascular events; pyridoxine in dose 7 mg/kg was found to be more potent than pyridoxine in doses 5, 10 mg/kg, amlodipine and isosorbide on vasopressin-induced angina in rats. Pyridoxine in dose of (5, 7 mg) prevents cardiac necrosis and artery well thickened on vasopressin-induced angina modal. Pyridoxine's protective effects may be mediated by improved endothelial nitric oxide synthase (eNOS) function, reduction of homocysteine levels, and modulation of sympathetic activity. Pyridoxine at optimal doses shows promise as a novel therapeutic agent for coronary heart disease prevention, warranting further investigation into its potential clinical applications.