ANTIHYPERTENSIVE POTENTIAL OF AQUEOUS EXTRACT OF Peristrophe bivalvis (L.) MERR. LEAF ON NG-NITRO L-ARGININE METHYL ESTER-INDUCED HYPERTENSION IN MALE WISTAR RATS

Abstract

Hypertension is a major risk factor for cardiovascular diseases. Most antihypertensive drugs have been reported to effectively reduce blood pressure (BP), but they do not ameliorate end-organ damage associated with hypertension. This necessitates the need for agents that can effectively manage hypertension and its complications. Peristrophe bivalvis (PB) is used in traditional medicine to treat hypertension and other ailments. This study was designed to investigate the effects of aqueous extract of PB leaf (APB) on NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension and its associated cardio-renal complications in male Wistar rats.

Peristrophe bivalvis leaf was obtained in Ikono, Akwa-Ibom State, and authenticated at the Department of Pharmacognosy and Herbal Medicine, University of Uyo (ID: UUHO43). Aqueous extract of PB leaf was obtained using cold maceration, filtration and concentration. Twenty-five male Wistar rats (150-170 g) were grouped into five (n=5). Group 1 received 10 mL/kg of distilled water (control) while groups 2-5 were administered with 60 mg/kg of L-NAME (L-NAME60, hypertensive [H]) orally for eight weeks to induce hypertension. After eight weeks, groups 2-5 received: L-NAME60+distilled water (hypertensive untreated [HuT]), L-NAME60+APB (200 mg/kg, hypertensive APB [HAPB]), L-NAME60+ramipril (10 mg/kg, hypertensive ramipril [HRM]) and distilled water (hypertensive recovery [R]) respectively, for five weeks. The BP was mea¬sured by tail-cuff method at 8th and 13th weeks of the study. The rats were sacrificed and samples (blood, heart and kidney) collected. Serum angiotensin II, cyclic Guanosine Monophosphate (cGMP), tissue Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor-alpha (TNF-α) levels were measured using ELISA technique. Tissue malondialdehyde, Superoxide Dismutase (SOD) and reduced Glutathione (GSH) levels were measured by spectrophotometry. Nitrotyrosine and Cluster of Differentiation 68 (CD68) expressions in the tissue were quantified using immunohistochemistry. Data were analysed using ANOVA at α0.05.

Systolic, diastolic and mean arterial BP significantly decreased in HAPB (161±1.30, 117±2.60, 132±1.60 mmHg), HRM (132±1.10, 100±1.10, 110±0.86 mmHg) and R (152±2.90, 117±2.30, 128±2.40 mmHg) groups compared to H (172±2.80, 131±2.50, 144±2.50 mmHg) and HuT (196±2.0, 159±2.80, 168±4.90 mmHg) groups, respectively. Angiotensin II level significantly decreased while cGMP level increased in HAPB group compared to HuT (32.49±0.45 vs 51.34±1.02 pmol/mL, 9.96±0.53 vs 6.50±0.62 pmol/mL, respectively). Levels of IL-1β (pg/g tissue) and TNF-α (ng/g tissue) in the heart (3609.33±372.18, 121.03±6.0) and kidney (4635.78±62.58, 174.79±16.92) of HAPB group significantly decreased relative to HuT heart (5157.11±113.66, 296.21±3.16) and kidney (5122.04±207.90, 289.99±6.17), respectively. Administration of L-NAME60+APB significantly decreased malondialdehyde (µmol/g tissue) level and increased SOD (units/g tissue) activity and GSH (mmol/g tissue) level in the heart (17.05±0.40, 2.50±0.05, 1.10±0.08) and kidney (15.43±0.63, 2.60±0.05, 1.20±0.06) compared to HuT heart (69.49±5.43, 0.39±0.03, 0.37±0.06) and kidney (61.39±4.80, 0.41±0.03, 0.44±0.07), respectively. Nitrotyrosine and CD68 expressions were decreased in the heart and kidney of HAPB group relative to HuT group. Blood pressure level significantly increased but nitrotyrosine expression in the heart decreased in HAPB group compared to HRM.