Modulation of endothelin system in blood pressure lowering mechanisms of piper sarmentosum aqueous extract in spontaneously hypertensive rat

Abstract

Cardiovascular diseases (CVD) are among the biggest contributors of global mortality, totalling around 17.7 million annually worldwide. Hypertension is considered as one of the key risk factors for CVD. The National Health and Morbidity Survey (NHMS) 2015 estimated that 30.3% of adults aged 18 years and above have hypertension, and that there is a rising trend in the prevalence of hypertension in adults aged 30 years or more. Moreover, among the treated patients, only 35% of them achieved target blood pressure of less than 140/90 mmHg despite established studies of the effectiveness of antihypertensive medications. One of the main reasons of treatment failure is patient compliance of the prescribed medications. Patients’ cultural belief of traditional therapy, stigma of conventional medicine, and drugs side effects contribute significantly to their compliance. Therefore, studies on alternative treatment such as local herbal remedies will be beneficial. Herbal medicines have been and are still used in some cultures for the treatment of hypertension and one of the plants is Piper sarmentosum (PS). PS or commonly recognized as kaduk in Malaysia, is known for its high antioxidant content. The antioxidant property of this plant is believed to be responsible for its antihypertensive property. This study was conducted to evaluate blood pressure reducing mechanism of Piper sarmentosum leaves aqueous extract (PSAE) through endothelial dysfunction amelioration. Blood pressure indices, level of mesenteric artery NO and endothelin 1 (ET-1), and proteomic expression of endothelin receptor subtype A (ETA receptor) by Western Blotting were studied in four different groups (n=6) of spontaneously hypertensive rats (SHRs). Two of the groups act as negative and positive control groups, receiving distilled water and 3 mg/kg Perindopril respectively. Another two groups are the treatment groups, which received Kadukmy™, and combination of 1.5 mg/kg Perindopril and Kadukmy™. Rats were treated for 28 consecutive days, and the blood pressure was measured weekly. Qualitative proteomic study of the ETA receptor was done and NO as well as ET-1 level were analysed at the end of treatment period, after the rats were humanely sacrificed. Findings from blood pressure indices showed that PSAE significantly reduced the systolic, diastolic, and mean arterial pressure (P<0.05). PSAE also increased NO level (P<0.05), reduced ET-1 level (P<0.05), and qualitatively downregulated mesenteric artery ETA receptor in the treatment group. These results suggested that PSAE reduced blood pressure in SHR by increasing NO production and reducing ET-1 level. Hence, mitigating endothelial dysfunction. Nevertheless, further investigations are needed to analyse the proteomic expression of ETA receptor quantitatively and further clarify the mechanisms involved in its downregulation.