¹Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia DOI : 10.35333/jrp.2020.122 Reduced endothelial nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) in the vasculature is a feature of endothelial dysfunction. Dexamethasone causes secondary hypertension by inhibiting eNOS activity. Piper sarmentosum is an herb with anti-hypertensive effect. The aim of this study was to evaluate the anti-hypertensive effect of aqueous extract of P. sarmentosum (AEPS) in dexamethasone (Dex)-induced hypertensive rats. A total of 30 male Sprague Dawley rats were divided into five groups including control, AEPS (500 mg/kg/day, orally), Dex (20 μg/kg/day, subcutaneously), Dex (20 μg/kg/day) + AEPS (500 mg/kg/day) and Dex (20 μg/kg/day) + captopril (40 mg/kg/day, orally). Blood pressure was measured using tail-cuff method at baseline and fortnightly thereafter. The rats were sacrificed and the serum was collected to quantify the amount of NO after 28 days of treatment. Aortic samples were homogenized for measurement of eNOS mRNA expression, protein level and activity. Treatment of Dex-induced hypertensive rats with AEPS lowered systolic blood pressure (P < 0.001) and diastolic blood pressure (P < 0.01), increased eNOS mRNA expression (P < 0.01), eNOS protein (P < 0.01), eNOS activity (P < 0.05) and NO level (P < 0.05). In conclusion, AEPS reduces the blood pressure of Dex-induced hypertensive rats as it shows positive effects on eNOS and NO production. Keywords : Dexamethasone; endothelial nitric oxide synthase; hypertension; nitric oxide; Piper sarmentosum