Ameliorative influence of co-administration of p-coumaric acid and lisinopril on blood pressure and crucial enzymes relevant to hypertension in L-arginine N-ω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension in rats

Augmenting the therapeutic effect of modern drugs with food rich in phenolic phytochemicals could be a novel strategy towards managing drug efficacy and ameliorating toxicity. This study aimed at examining the combined treatment effect of p-coumaric acid, a phenolic compound with lisinopril on blood pressure and crucial enzymes relevant to hypertension in L-arginine N-ω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Oral daily administration of L-NAME (40 mg/kg) for 14 days was used to induce hypertension in rats. Hypertensive rats were treated with p-coumaric acid (50 mg/kg and 100 mg/kg) and/or lisinopril (10 mg/kg) via oral administration for 14 sequential days. Subsequently, the alterations in blood pressure were determined and histology of the heart tissue was carried out. Hypertensive rats showed significantly (p < 0.05) higher ACE, arginase, acetylcholinesterase, and phosphodiesterase-5 activities and lipid peroxidation (LPO) level as well as significantly (p < 0.05) lower nitric oxide (NO) level when compared with the control. Nevertheless, a combination of p-coumaric acid and lisinopril managed hypertension with a reduction in ACE, acetylcholinesterase, arginase, and phosphodiesterase-5 activities caused a decline in LPO level and amplified levels of NO in comparison with the hypertensive rats. The histological architecture of the hypertensive rat heart treated with p-coumaric acid and/or lisinopril showed mild to near normal structures of epicardium, myocardium, and endocardium. This study suggests that the combination of lisinopril with p-coumaric acid may significantly influence the antihypertensive properties of lisinopril and provide a drug-food interaction model towards the management of hypertension. © The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2024.