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Objectives: This study aims to investigate the anti-hypertensive effects of aqueous extract of Callisia fragrans and their underlying mechanism using a two-kidney one-clip (2K1C) model of reno-vascular hypertension in rats., Methods: The reno-vascular hypertensive rats were treated with C. fragrans leaf extract (100 and 500 mg/kg; p.o.) and a reference drug, captopril (20 mg/kg; p.o.), for 4 weeks. The blood pressure and heart rate were recorded using a tail-cuff. The heart weight, left ventricular wall thickness, and serum creatinine and urea levels were measured. A spectrophotometric assay was used to analyze the angiotensin-converting enzyme (ACE) inhibition activity of the extract and the reference drug. The total volume and the concentration of sodium, potassium, and chloride in urine samples were evaluated., Results: C. fragrans extract significantly reduced both systolic and diastolic blood pressures in the reno-vascular hypertensive rats. No significant difference in the heart rate was observed between each animal group. C. fragrans extract reduced the 2K1C-induced increase in the heart and body weight ratio and the left ventricular wall thickness. Moreover, the extract also attenuated the increase in serum urea induced by the 2K1C treatment. C. fragrans extract inhibited ACE activity in vitro with an IC 50 of 20.97 ± 3.94 µg/ml. The urine output and urinary electrolyte excretion significantly increased in C. fragrans extract-treated rats., Conclusions: These findings demonstrated that C. fragrans extract can mitigate hypertension and alleviate ventricular hypertrophy and renal dysfunction in reno-vascular hypertensive rats, at least in part via ACE activity inhibition and diuretic property.

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a protein kinase that inactivates eEF2, a protein that mediates a peptidyl-tRNA translocation during an elongation step of protein synthesis. We have previously shown that eEF2K was involved in pathogenesis of essential and pulmonary hypertension. A484954 (7-amino-1-cyclopropyl-3-ethyl-2,4-dioxo-1,2,3,4- tetrahydropyrido[2,3-d] pyrimidine-6-carboxamide), a selective eEF2K inhibitor, is a membrane permeable small molecule. We have previously shown that A484954 lowered blood pressure and induced diuretic effects in spontaneously hypertensive rats (SHR) due to an increase in renal blood flow. Here we aimed to reveal mechanisms underlying the diuretic effects of A484954 in SHR. A484954-induced diuresis and increase in urinary Na+ excretion were inhibited by N (G)-nitro-Larginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor. A484954 increased mRNA expression of angiotensin type 2 receptor (AT2R) and nuclear factor-erythroid 2-related factor 2 (Nrf2). In summary, we for the first time revealed that A484954 induces diuresis in SHR at least partly via the activation of NO/Nrf2/AT2R pathway. [ABSTRACT FROM AUTHOR]

Abstract: We evaluate the short-term effect of a Fraxinus excelsior L. seed extract, named FraxiPure (FRP) on spontaneously hypertensive rats (SHR). Water, Captopril and different doses of FRP were orally administered. Blood pressure was recorded by the tail cuff method and plasma samples were collected to determine antioxidant capacity and malondialdehyde equivalents. In other trials, 18h fasted SHR were administered water, FRP, Furosemide, Torasemide, and Captopril. In these animals, urine was collected for 4h to obtain the urine volumetric excretion (UVE). Plasma samples of these animals were used to establish the fractional excretion (FE) of different ions (Na+, Cl−, K+, Ca2+ and PO4 3−) and metabolites (creatinine, urea and uric acid). FRP shows antihypertensive effect. The decrease in blood pressure caused by FRP was slightly lower than that of Captopril and more accentuated than that of Torasemide. FRP and Torasemide significantly increased UVE. Torasemide significantly increased FE(Na+) and FE(Cl−) and showed a clear uricosuric effect. FRP showed slight natriuretic effects and behaved as a potassium-sparing diuretic. FRP significantly increased plasma antioxidant capacity and decreased plasma malondialdehyde equivalents. The antihypertensive effect of FRP in SHR can therefore be related with its diuretic and antioxidant properties. [Copyright &y& Elsevier]

Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly. [ABSTRACT FROM AUTHOR]