Antihypertensive effect of the stem bark aqueous extract of Garcinia lucida Vesque (Clusiaceae) in L-NAME-treated rats: Contribution of endothelium-dependent and -independent vasorelaxation.

Garcinia lucida is used in Cameroonian folk medicine to handle a variety of ailments, including arterial hypertension. This study aimed at determining the phytochemical profile and the antihypertensive effect of the stem bark aqueous extract of G. lucida (AEGL). AEGL was subjected to LC-MS analysis, and its effect (75, 150, and 300 mg/kg/day; by gavage) was evaluated against Nω-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg)-induced hypertension in adult male Wistar rats for four consecutive weeks. Blood pressure and heart rate were monitored weekly using tail-cuff plethysmography. The vasorelaxant effect of cumulative concentrations (3-10-30-100-300 µg/mL) of AEGL was examined on endothelium-intact and denuded thoracic aorta rings which were precontracted with KCl (90 mM) or norepinephrine (NE; 10-5 M), and in the absence or presence of L-NAME (10-4 M), indomethacin (10-5 M), methylene blue (10-6 M), tetraethylammonium (TEA, 5 × 10-6 M), glibenclamide (10 × 10-6 M) or propranolol (5 × 10-6 M). The influence of AEGL on the response to NE, KCl, and CaCl2 was also investigated. Six compounds, including Garcinia biflavonoids GB1 and GB2, were identified. AEGL prevented the development of hypertension (p < 0.01 and p < 0.001) without affecting the heart rate. AEGL induced a concentration-dependent relaxation of aortic rings precontracted with NE (EC50 = 7.915 µg/mL) that was significantly inhibited by the removal of the endothelium, L-NAME, or methylene blue (p < 0.05-0.001). Indomethacin, propranolol, TEA, and glibenclamide did not affect AEGL-evoked vasorelaxation. Preincubation of aortic rings with AEGL reduced the magnitude of contraction elicited by CaCl2 but did not alter that of KCl or NE. AEGL possesses an antihypertensive effect that is mediated by both endothelium-dependent and endothelium-independent mechanisms. The activation of the NO/sGC/cGMP pathway accounts for the endothelium-dependent vasorelaxation. These pharmacological effects of AEGL could be attributed to the presence of the Garcinia biflavonoids GB1 and GB2.

Vasorelaxant-Mediated Antihypertensive Effect of the Leaf Aqueous Extract from Stephania abyssinica (Dillon & A. Rich) Walp (Menispermaceae) in Rat.

Stephania abyssinica is a medicinal plant used in Cameroon alternative medicine to treat arterial hypertension (AHT). Previous in vitro studies demonstrated the endothelium nitric oxide-independent vasorelaxant property of the aqueous extract from Stephania abyssinica (AESA). But its effect on AHT is unknown. The present study was undertaken to explore other vasorelaxant mechanisms and to determine the antihypertensive effects of AESA in male Wistar rats. Phytochemical analysis of AESA was carried out using the liquid chromatography-mass spectrometry (LC-MS) method. The vasorelaxant effects of AESA (1-1000 µg/mL) were studied on rat isolated thoracic aorta rings, in the absence or presence of indomethacin (10 µM) or methylene blue (10 µM). The inhibitory effect of AESA on phenylephrine (PE, 10 µM) or KCl- (60 mM) induced contraction as well as the intracellular calcium release was also evaluated. The in vivo antihypertensive activity of AESA (43, 86, or 172 mg/kg/day) or captopril (20 mg/kg/day) administered orally was assessed in L-NAME- (40 mg/kg/day) treated rats. Blood pressure and heart rate (HR) were measured at the end of each week while serum or urinary nitric oxide (NO), creatinine, and glomerular filtration rate (GFR) were determined at the end of the 6 weeks of treatment, as well as histological analysis of the heart and the kidney. The LC-MS profiling of AESA identified 9 compounds including 7 alkaloids. AESA produced a concentration-dependent relaxation on contraction induced either by PE and KCl, which was significantly reduced in endothelium-denuded vessels, as well as in vessels pretreated with indomethacin and methylene blue. Moreover, AESA inhibited the intracellular Ca2+ release-induced contraction. In vivo, AESA reduced the AHT, heart rate (HR), and ventricular hypertrophy and increased serum NO, urine creatinine, and GFR. AESA also ameliorated heart and kidney lesions as compared to the L-NAME group. These findings supported the use of AESA as a potential antihypertensive drug.

Antihypertensive Effects of the Methanol Extract and the Ethyl Acetate Fraction from Crinum zeylanicum (Amaryllidaceae) Leaves in L-NAME-Treated Rat.

Arterial hypertension (AHT) is a leading cardiovascular disease, with a high negative impact on the quality of life. Crinum zeylanicum (C. zeylanicum) leaves extract is used in the West region of Cameroon to treat AHT and heart problems. This study aimed to investigate the antihypertensive effect of C. zeylanicum extract in N ω -nitro-L-arginine methyl ester- (L-NAME-) induced hypertensive rats. The aqueous extract of C. zeylanicum (LAE) was obtained by lyophilizing the juice of triturated fresh leaves. The methanol extract (LME) prepared by maceration of the dried leaves was further partitioned to chloroform (LCF), ethyl acetate (LEAF), and residual (LRF) fractions. The total polyphenol, flavonoid content, and antiradical potentials of these extracts were determined. The curative antihypertensive and renal function protective effects of LME and LEAF were evaluated in vivo on L-NAME-induced hypertensive rats. Hypertension was induced in rats by oral administration of L-NAME (30 mg/kg/day) for 3 consecutive weeks. Thereafter, plant extracts were administered orally at the doses of 30, 60, and 120 mg/kg/day, concomitantly with L-NAME for three other weeks. Body weight, heart rate, and arterial blood pressure were measured at the end of each week throughout the experimental period. At the end of the treatment, 24-hour urine and plasma were collected to assay nitric oxide (NO), creatinine, and protein. The results revealed that LEAF has the higher content of total polyphenol and flavonoid and exhibited the best antiradical potential. Moreover, treatment of hypertensive rats with LME and LEAF significantly (p < 0.001) reduced AHT and heart rate. LME and LEAF significantly increased rat's body mass, plasmatic NO, and urinary creatinine and reduced urine NO and protein contents as compared to the L-NAME group. LME and its LEAF possess potent antihypertensive effects and further protect the renal function in L-NAME-induced hypertensive rats, thus supporting the use of C. zeylanicum in the management of AHT.

Endothelium nitric oxide-independent vasorelaxant effects of the aqueous extract from Stephania abyssinica on the isolated rat thoracic aorta.

BACKGROUND: Stephania abyssinica (Dillon & A. Rich) Walp (Menispermaceae) is a medicinal plant used in the west region of Cameroon to treat arterial hypertension. The present study evaluated the vasorelaxant effects of the aqueous (AESA) and methanol (MESA) extracts from the fresh leaves of S. abyssinica on aorta rings isolated from Wistar rats. METHODS: Aorta rings with intact endothelium were contracted with KCl (60 mM) or phenylephrine (10-5 M) and exposed to cumulative concentrations of each extract, ranging from 10 to 1,000 µg/mL. The vasorelaxant effects of AESA were further evaluated in presence of Nω-nitro-L-arginine methyl ester (L-NAME, 10-4 M), tetraethylammonium (TEA, 5 µM), glibenclamide (5 µM), propranolol (5 µM), and the association glibenclamide-propranolol (AGP). In another set of experiments, the effect of AESA was evaluated on calcium-induced contraction in a hyperpotassic milieu. RESULTS: AESA and MESA exhibited a concentration-dependent vasorelaxation on KCl-contracted aortic rings with respective EC50 of 160.10 and 346.50 µg/mL. AESA similarly relaxed aortic rings contracted with phenylephrine (EC50, 176.80 µg/mL). The vasorelaxant activity of AESA was not significantly affected by L-NAME but was markedly reduced by TEA, glibenclamide, propranolol, and AGP. AESA strongly inhibited the Ca2+-induced contraction by 95%. CONCLUSIONS: These results support the use of S. abyssinica against arterial hypertension and suggest that the vasorelaxant effect of AESA is not mediated via the endothelium/nitric oxide pathway. AESA relaxant properties might be due to an inhibition of Ca2+ influx and/or the activation of ATP-sensitive K+ channels probably via the stimulation of ß-adrenergic receptors.