Preventive beneficial effect of an aqueous extract of Phyllanthus amarus Schum. & Thonn. (Euphorbiaceae) on DOCA-salt-induced hypertension, cardiac hypertrophy and dysfunction, and endothelial dysfunction in rats.

This study investigated the preventive effect of an aqueous extract of the whole plant of Phyllanthus amarus (AEPA) on blood pressure, cardiac and endothelial function in the deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rat model. Male Wistar rats were assigned into five groups receiving either vehicle (control and DOCA-salt), DOCA-salt combined with AEPA at 100 or 300 mg/kg, or AEPA (100 mg/kg) alone for 5 weeks. In addition, DOCA-salt-treated rats were allowed free access to water containing 1% NaCl. Systolic blood pressure (SBP), left ventricle parameters, vascular reactivity of primary mesenteric artery rings, the vascular level of oxidative stress and the level of target proteins were determined, using respectively tail-cuff sphygmomanometry, echocardiography, organ chambers, dihydroethidium staining, and immunofluorescence methods. After 5 weeks, AEPA treatments (100 or 300 mg/kg/day) significantly prevented the increase in SBP in DOCA-salt rats, respectively by about 24 and 21 mmHg, improved cardiac diastolic function, and reduced significantly the increased posterior and septum diastolic wall thickness and the left ventricle mass in hypertensive rats. Moreover, the DOCA-salt-induced endothelial dysfunction, and the blunted nitric oxide- and endothelium-dependent hyperpolarization-mediated relaxations in primary mesenteric artery were improved after the AEPA treatments. AEPA also reduced the level of vascular oxidative stress and the expression level of target proteins (eNOS, COX-2, NADPH oxidase subunit p22) in DOCA-salt rats. Altogether, AEPA prevented hypertension, improved cardiac structure and function, and endothelial function in DOCA-salt rats. Such beneficial effects appear to be related, at least in part, to normalization of the vascular level of oxidative stress.