OBJECTIVES: To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats.
METHODS: Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5-20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro.
RESULTS: Intravenous administrations of butanolic fraction elicited significant (p < 0.001) and dose-dependent decreases in the mean arterial pressure. However, a significant (p < 0.05) decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg). In isolated preparations of rat aortic rings, phenylephrine (1 × 10⁻⁶ M)- or potassium chloride (8 × 10⁻² M)-precontracted endothelium-intact and -denuded tissue; butanolic fraction (1 × 10⁻⁶ - 1 × 10⁻¹ g/ml) induced similar concentration-dependent relaxation of the vessels. In the presence of 2.5 × 10⁻³ and 5.0 × 10⁻³ g/ml butanolic fraction, the contractions induced by phenylephrine (1 × 10⁻⁹-3 × 10⁻⁵ M) and potassium chloride (1 × 10⁻² - 8 × 10⁻² M) were significantly antagonized. The calcium-induced vasocontractions (1 × 10⁻⁴-1 × 10⁻²M) were antagonized by butanolic fraction concentration-dependently in calcium-free and high potassium (6×10⁻² M) medium, as well as in calcium- and potassium-free medium containing 1×10⁻⁶ M phenylephrine. However, the contractions induced by noradrenaline (1 × 10⁻⁶ M) and caffeine (4.5 × 10⁻² M) were not affected by butanolic fraction.
CONCLUSION: Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and/or voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.
METHODS: Extracts of ZOVR were subjected to in-vivo antihypertensive screening using noninvasive blood pressures in SHRs. The most potent extract, ZOVR petroleum ether extract (ZOP) was then fractionated using n-hexane, chloroform and water. Isolated thoracic aortic rings were harvested and subjected to vascular relaxation studies of n-hexane fraction of ZOP (HFZOP) with incubation of different antagonists such as Nω-nitro-l-arginine methyl ester (L-NAME, 10 µmol/L), indomethacin (10 µmol/L), methylene blue (10 µmol/L), atropine (1 µmol/L), glibenclamide (10 µmol/L), prazosin (0.01 µmol/L), and propranolol (1 µmol/L).
RESULTS: During the screening of various ZOVR extracts, ZOP produced the most reduction in blood pressures of SHRs and so did HFZOP. HFZOP significantly decreased phenylephrine-induced contraction and enhanced acetylcholine-induced relaxation. L-NAME, indomethacin, methylene blue, atropine, and glibenclamide significantly potentiated the vasorelaxant effects of HFZOP. Propranolol and prazosin did not alter the vasorelaxant effects of HFZOP. HFZOP significantly suppressed the Ca2+-dependent contraction and influenced the ratio of the responses to phenylephrine in Ca2+-free medium.
CONCLUSION: This study demonstrates that ZOP may exert an antihypertensive effect in the SHR model. Its possible vascular relaxation mechanisms involve nitric oxide and prostacyclin release, activation of cGMP-KATP channels, stimulation of muscarinic receptors, and transmembrane calcium channel or Ca2+ release from intracellular stores. Possible active compounds that contribute to the vasorelaxant effects are 6-gingerol, 8-gingerol and 6-shogaol.
AIM OF THE STUDY: This study was carried out to investigate the antihypertensive and vasodilatory activity of four solvents extracts of P. niruri namely; petroleum ether (PEPN), chloroform (CLPN), methanol (MEPN) and water (WEPN), with the aim of elucidating the mechanism of action and identifying the phytochemical constituents.
MATERIALS AND METHODS: Male Spontaneous Hypertensive Rats (SHRs) were given oral gavage of P. niruri extract daily for two weeks and the blood pressure was recorded in vivo. We also determine the vasodilation effect of the extracts on rings of isolated thoracic aorta pre-contracted with phenylephrine (PE, 1 μM). Endothelium-intact or endothelium-denuded aorta rings were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM) and Methylene blue (MB 10 μM), sGC inhibitors; Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 μM) a nitric oxide synthase (NOS) inhibitor; atropine (10 μM), a cholinergic receptor blocker; indomethacin (10 μM), a cyclooxygenase inhibitor and various K+ channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study.
RESULTS: SHRs receiving P. niruri extracts showed a significant decrease in their blood pressure (BP) when compared to the baseline value, with PEPN being more potent. The extracts (0.125-4 mg/mL) also induced vasorelaxation on endothelium-intact aorta rings. PEPN elicited the most potent maximum relaxation effect (Rmax). Mechanism assessment of PEPN showed that its relaxation effect is significantly suppressed in endothelium-denuded aorta rings. Pre-incubation of aorta rings with atropine, L-NAME, ODQ, indomethacin, and propranolol also significantly attenuated its relaxation effect. Conversely, incubation with TEA and glibenclamide did not show a significant effect on PEPN-induced relaxation.
CONCLUSION: This study indicates that the antihypertensive activity of P. niruri extract is mediated by vasoactive phytoconstituents that dilate the arterial wall via endothelium-dependent pathways and β-adrenoceptor activity which, in turn, cause vasorelaxation and reduce blood pressure.
AIM OF THE STUDY: Chemico-biological standardization with respect to its vasorelaxation potential is the main objective of the present study. To investigate the vasorelaxation potential of key phytochemical of KGR, i.e., ethyl-p-methoxycinnamate (EPMC) and to study it's the mechanism of action.
MATERIALS AND METHODS: A HPLC method was developed and validated for the quality assessment of KGR using its two major phytochemicals i.e. ethyl-p-methoxycinnamate (EPMC) and ethyl cinnamate (EC) in KGR. The vasorelaxation effect of major phytochemicals of KGR was evaluated on the main mesenteric arteries isolated from male Wistar rats. Specific BKca channel blocker tetraethylammonium (TEA), receptor antagonist, nitric oxide scavenging capacity, and antioxidant potential were also evaluated for its plausible mechanism.
RESULTS: Present validated HPLC method facilitates simultaneous quantitation of EPMC and EC faster than classical GC techniques. EPMC has shown a dose-dependent relaxation in rat main mesenteric arteries (MMA) contracted by U46619 with an Emax of 58.68 ± 3.31%. Similarly, in endothelium-denuded MMA rings, relaxation was also observed (Emax of 61.83 ± 3.38%). Moreover, relaxation response to EPMC has strongly inhibited (Emax 14.76 ± 2.29%) when the tissue exposed to depolarizing high K+ containing buffer for the contraction. The point correlation dimension (pD2) values were also significantly decreased in high K+ treated arterial rings compared to control. Interestingly, when MMA rings incubated with a specific BKca channel blocker (TEA, 1 mM), the relaxation response to EPMC was also significantly blocked.
CONCLUSIONS: The first time this study demonstrated the chemical standardization of K. galanga rhizome and EPMC is responsible for its vasorelaxation potential as demonstrated by the endothelium-independent response mediated by Ca2+ dependent potassium channels.
METHODS: A single-arm multicenter prospective study was designed aiming to determine the safety and efficacy of ESMT. Patients of functional Canadian Cardiovascular Society class II-IV, despite stable and optimal medical management, with documented myocardial segments with reversible ischemia and/or hibernation on the basis of echocardiography/single-photon emission computerized tomography (SPECT) were enrolled from 2010 to 2012. A total of 111 patients were enrolled, 33 from Indonesia, 21 from Malaysia, and 57 from Philippines. Patients underwent nine cycles of ESMT over 9 weeks. Patients were followed up for 3-6 months after ESMT treatment. During follow-up, patients were subjected to clinical evaluation, the Seattle Angina Questionnaire, assessment of nitrate intake, the 6-min walk test, echocardiography, and SPECT.
RESULTS: The mean age of the population was 62.9±10.9 years. The summed difference score on pharmacologically induced stress SPECT improved from 9.53±17.87 at baseline to 7.77±11.83 at follow-up (P=0.0086). Improvement in the total Seattle Angina Questionnaire score was seen in 83% of patients (P<0.0001). Sublingual nitroglycerin use significantly decreased (1.14±1.01 tablets per week at baseline to 0.52±0.68 tablets per week at follow-up; P=0.0215). There were no changes in left ventricular function on echocardiography (0.33±9.97, P=0.93). The Canadian Cardiovascular Society score improved in 74.1% of patients.
CONCLUSION: This multicenter prospective trial demonstrated that ESMT is both a safe and an efficacious means of managing medically refractory angina.