The well known metabolic functions of L-arginine have been recently increased with the discovery of its role as the substrate for the synthesis of nitric oxide (NO), which has emerged as an endogenous signaling molecule with potential therapeutic implications for cardiovascular disease. Steady-state levels of NO are derived in part from dietary sources. It has been reported that supplementation of L-arginine reduces atherosclerosis in rabbits and reduces the arterial pressure in hypertensive rats. Therefore, we investigated the effect of L-arginine supplementation using a group of induced hypercholesterolemic rats and a group of spontaneously hypertensive rats; the infarcted area in cardiac tissue of both groups was measured during the response to myocardial infarction in the ischemia-reperfusion model. Hypercholesterolemic rats supplemented with 170 mg kg⁻¹ of L-arginine showed a significant (P ≤ 0.05) reduction in total cholesterol (25.2%) and LDL (27.8%). Spontaneously hypertensive rats supplemented with L-arginine presented a significant reduction (20.3%) in mean blood pressure (P ≤ 0.05). The index infarcted area / total heart area, in both: hypercholesterolemic and hypertensive rats supplemented with L-arginine, showed a significant 36% and 29% of cardio protection (P ≤ 0.05) effect, respectively. Dietary supplementation with L-arginine may represent a potentially novel nutritional strategy for the treatment of cardiovascular disease.