[show abstract][hide abstract] ABSTRACT: The vasodilatory effect of tetrazepam was investigated using isolated rat and rabbit thoracic aortic rings and compared with the effect of diltiazem in both vessels.Aortic rings were precontracted with potassium chloride (60 mM) or phenylephrine (3 times 10−8 M in rat and 3 times 10−6 M in rabbit aortic rings). Tetrazepam produced similar concentration-dependent relaxation in aortic rings with and without endothelium, and completely inhibited rat aortic rings precontracted with phenylephrine or KCl but produced no effect on phenylephrine-induced contraction in rabbit aorta. These effects are similar to those obtained with diltiazem, although, in all other respects diltiazem was more potent. The IC50 value for tetrazepam in KCl- or phenylephrine-contracted aortic rings was 12 mM or 5.9 mM, respectively, which is above the range of therapeutic plasma concentrations of the benzodiazepines (10−7–10−5 M).We conclude that vasodilation produced by tetrazepam is not endothelium-dependent and tetrazepam may act as a Ca2+-channel blocker like diltiazem.
Pharmacy and Pharmacology Communications. 03/2011; 2(10):495 - 497.
[show abstract][hide abstract] ABSTRACT: Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.
Mini Reviews in Medicinal Chemistry 03/2011; 11(4):298-344. · 2.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effects of two monounsaturated fatty acid (MUFA)-rich diets, containing virgin olive oil (OO) and high-oleic-acid sunflower oil (HOSO), on development of vascular response from isolated thoracic rat aorta and lipid composition and fatty acid composition were studied and compared with samples from rats fed on a control diet. Dietary MUFA oils were fed for 6 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 weeks of age. The maximum contraction of aortic ring preparations in response to phenylephrine (10(-6) m) was significantly decreased in SHR rats fed with OO (0.81 (sem 0.05) v. 1.18 (sem 0.09) g, and treatment with HOSO did not alter the phenylephrine-induced contractions. The relaxant responses to acetylcholine (10(-5) m) were significantly enhanced (30.03 (sem 0.70) v. 18.47 (sem 0.28) %, in the rings from SHR rats treated with OO, and were more pronounced than in WKY rats In the same way, OO attenuated the dose-response curves induced by phenylephrine (10(-8)-10(-5) m) from SHR rats, accompanied with a slower contraction. These results suggest that only the chronic feeding of OO diet was able to attenuate the vascular response of rat aorta. In addition, an increase in phospholipid content (186.7 (sd 3.2) v. 159.1 (sd 11.3) g/kg, and changes in the fatty acid composition of aorta (mainly a decrease in arachidonic acid) could contribute to improving endothelial function. Therefore, the effects can not be attributed exclusively to the content of MUFA (mainly oleic acid). Other components of OO, such as polyphenols, not present in HOSO, may help to explain the vascular protective effect of OO consumption.
British Journal Of Nutrition 10/2001; 86(3):349-57. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cecropia obtusifolia (Cecropiaceae) is a species from tropical America and its leaves are used in traditional medicine for the treatment of diabetes and as an anti-inflammatory agent. In the present study, the analgesic, anti-inflammatory and central nervous system depressant effects of the aqueous extract from the leaves of C. obtusifolia were investigated in different experimental models, with the purpose of validating its ethnomedical uses. The results obtained with the extract from the leaves of C. obtusifolia reflect a low toxicity, a substantial central depressor effect and analgesic activity and significant motor incoordination and muscle relaxant activity. Concerning the analgesic activity, using the hot plate test, the extract did not produce any effect, however it showed a significant effect on the pain induced by chemical stimuli (acetic and formalin test); this suggests the peripheral analgesic effect of the extract. The extract also showed a topical and systemic anti-inflammatory effect. Thus this work could justify the popular use of C. obtusifolia in rheumatic and kidney inflammation pathologies and reveals that this plant is an interesting species.
Journal of Ethnopharmacology 09/2001; 76(3):279-84. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: This report is focused on the study of simvastatin-induced relaxation of rat aorta through its effects on vascular smooth muscle and Ca(2+) signalling. The presence of endothelium affected only the simvastatin-induced relaxation of aortic rings precontracted with noradrenaline, but not by depolarization with KCl 80 mM. Blockade of Ca(2+) entry through voltage-operated Ca(2+) channels (VOCCs) by diltiazem abolished the endothelium-dependent and direct relaxation, whereas Ca(2+)-ATPase inhibition by cyclopiazonic acid (3 x 10(-5) M) only affected the endothelium-dependent relaxation. In KCl-depolarised arteries concentration-response curves for CaCl(2) were shifted to the right in the presence of simvastatin (3 x 10(-6) and 3 x 10(-5) M) or diltiazem (10(-6) and 10(-7) M). The transient contraction caused by noradrenaline in Ca(2+)-free medium, which is mainly due to intracellular Ca(2+) release, was inhibited by simvastatin (3 x 10(-5) M) or cyclopiazonic acid (3 x 10(-5) M) and the contraction induced by CaCl(2) (2 x 10(-3) M) added after noradrenaline was inhibited by diltiazem and simvastatin. All the reported effects of simvastatin were inhibited by the product of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, mevalonate (10(-3) M). These findings demonstrate that the vascular effects of simvastatin may involve both Ca(2+) release from intracellular stores, which could promote activation of endothelial factors, and blockade of extracellular Ca(2+) entry, which promote relaxations independent of the presence of endothelium. This action on Ca(2+) could be related to the inhibition of isoprenoid synthesis, which subsequently affects the function of G-proteins involved in communication among intracellular Ca(2+) pools and capacitative Ca(2+) entry.
European Journal of Pharmacology 04/2001; 415(2-3):217-24. · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the effects of chronic treatment with simvastatin (SV) on endothelium-dependent relaxation and ouabain-induced contractions in aortic rings from spontaneously hypertensive rats (SHR), comparing with normotensive Wistar-Kyoto rats (WKY).
After a 12-week period of administration of 1 or 2 mg/kg SV to SHR and WKY, systolic blood pressure (SBP) and vascular reactivity in endothelium-intact aortic rings were assessed.
Relaxation in response to acetylcholine (ACh) in WKY remained unaltered, but in SHR treated with 1 mg/kg SV, enhanced ACh-induced relaxation (P<0.05 versus untreated SHR) reached values observed in untreated WKY. The 2 mg/kg treatment also improved ACh relaxation (P<0.01 and P<0.05 versus untreated SHR and WKY respectively). Inhibiting cyclo-oxygenase (COX) with indomethacin (INDO) improved ACh relaxation in SHR (P<0.05) but not in WKY, independent of treatment with SV. Inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine (L-NOARG) abolished ACh relaxations in all cases (P<0.001). The result was unaltered when combining INDO plus L-NOARG. SV treatment also decreased ouabain-induced contractions in endothelium-intact aortic rings from SHR, diminishing the percentage effect of contraction from 64.56+/-2.95 (untreated SHR) to 26.98+/-7.06 and 38.10+/-8.21 (1 and 2 mg/kg treated SHR respectively). Response to ouabain in WKY was not significantly affected by SV treatment
Chronic treatment of SHR with SV improves endothelium-dependent ACh relaxation of the aortic rings, probably by an NO-involving mechanism more than by inhibiting contractile COX-derived factors. An improvement in endothelial modulation of ouabain-induced contractions was also observed after treatment with SV in SHR, which might be due to an inhibition of a calcium-sodium exchanger.
Journal of Hypertension 06/1999; 17(6):769-76. · 3.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: The vasodilating effects of tetrazepam (1,4-benzodiazepine derivative) were studied and compared with those of the K-channel activator, cromakalim and the Ca-channel blocker, diltiazem, in rat aorta smooth muscle and on the spontaneous contractile activity of the rat portal vein. In the aorta, tetrazepam (3 x 10(-7)-10(-4) M) and diltiazem (10(-8)-3 x 10(-6) M) concentration-dependently relaxed aortic rings contracted by 30 mM as well as 80 m KCl. Although cromakalim (10(-8)-3 x 10(-6) M) concentration-dependently relaxed aortic rings contracted by 30 mM KCl, it did not relax those contrated by 80 mm KCl. In the presence of the ATP-sensitive K-channel blocker, glibenclamide (10(-6) and 3 x 10(-6) M), 30 mM KCl concentration-response curves for the relaxant effect of tetrazepam and diltiazem were unaffected but cromakalim caused a progressive shift of these curves upwards. In the portal vein, tetrazepam inhibited spontaneous contractions, decreased amplitude and increased frequency. Similar behaviour was shown with diltiazem (10(-8)-10(-5) M) and in both cases, pre-treatment with glibenclamide (10(-6) M) was ineffective. Although cromakalim (10(-5)-10(-6) M) decreased both amplitude and frequency, this effect was blocked by glibenclamide. These results indicate that the vasodilator action of tetrazepam is not mediated to the opening of ATP-sensitive K-channels, unlike cromakalim. This may be mediated, like those of diltiazem, by the blockade of calcium movements across the cell membrane.
Pharmacological Research 10/1997; 36(3):237-42. · 4.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was designed to examine the inhibitory effects exerted by tetrazepam isolated rat duodenum and guinea pig ileum contractive responses and to further clarity the mechanisms involved. Tetrazepam produced concentration-dependent and complete relaxation of muscle contractions induced by KCl (80 mM) in guinea-pig ileum and this relaxant action was not antagonized by pretreatment with hexamethonium (0.1 mM), antagonist for nicotinic receptors, or atropine (1 microM), antagonist for muscarinic receptors, or PK 11195 (1 microM) antagonist for peripheral-type benzodiazepines receptors. Tetrazepam also modified the concentration-response curves of CaCl2 in calcium-free and high K/ depolarizing medium as soon as concentration-response curves of acetylcholine in Tyrode solution. The results suggested that tetrazepam inhibits the contractile responses to guinea-pig ileum and rat duodenum, probably through a reduction of calcium influx by way of calcium channels and these events are not related to high-affinity peripheral benzodiazepine binding sites.
Pharmacological Research 06/1997; 35(5):493-7. · 4.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was designed to determine the gastroprotective properties of naringin on and the involvement of endogenous prostaglandins in mucosal injury produced by absolute ethanol. Oral pretreatment with the highest dose of naringin (400 mg/kg), 60 min before absolute ethanol was the most effective antiulcer treatment. Subcutaneous administration of indomethacin (10 mg/kg) to the animals treated with naringin (400 mg/kg) partially inhibited gastric protection, but the prostaglandin E2 determination did not show any increase in prostanoid levels. The contents of gastric mucus and total proteins were not significantly modified. Naringin-treated rats showed a marked increase in hexosamine levels, but this increase was less in animals pretreated with indomethacin. These results show that naringin has a 'cytoprotective' effect against ethanol injury in the rat, but this property appears to be mediated by non-prostaglandin-dependent mechanisms.
[show abstract][hide abstract] ABSTRACT: Simvastatin is an inhibitor of HMG-CoA reductase used in the treatment of hypercholesterolemia. In the present study simvastatin-induced contraction was observed in rat aortic thoracic rings, this effect increased when the endothelium was removed and when NO synthase was blocked by L-NOARG (3 x 10(-5) M). The contractile effect of simvastatin on intact aortic rings diminished when cyclo-oxygenase was inhibited with indomethacin (10(-5) M). Also in the presence of endothelium, pretreatment with mevalonate (1 mM), the product of HMG-CoA reductase activity, significantly inhibited the contraction. In other experiments carried out on endothelium-removed preparations and in medium containing the calcium antagonist, diltiazem (10(-5) and 10(-6) M), the contraction dose-response curves were significantly reduced and the same happened in the presence of the inhibitor of sarcoplasmic reticulum Ca-2+-ATPase, cyclopiazonic acid (CPA) (3 x 10(-6) M). The results suggest that simvastatin might increase intracellular calcium concentration. This effect could lead to an activation of NO synthase and cyclooxygenase pathways in endothelial cells and to contraction in vascular smooth muscle cells. This rise in Ca2+ concentration could be due to an inhibition of isoprenoid synthesis prevented by mevalonate.
Zeitschrift fur Naturforschung C 55(1-2):121-4. · 0.60 Impact Factor