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Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca2+ signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights 1) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca2+ uniporter (MCU) enhance Ca2+-dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. 2) Female VSMCs have lower cytosolic Ca2+ levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α1C (CaV1.2), Na+-K+-2Cl− symporter (NKCC1), and the Na+/K+-ATPase. 3) When compared with androgens, the influence of estrogens on Ca2+ homeostasis, vascular tone, and incidence of vascular disease is better documented. 4) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. 5) Sex-dependent differences in Ca2+ signaling mean both sexes ought to be included in experimental design. [ABSTRACT FROM AUTHOR]

Drimys winteri J.R. Forst. & G. Forst (D.C) G. Gray, var. chilensis (canelo) is an endemic tree from Chile. Since pre-Columbian times, it has produced a fruit known as the canelo pepper, (pimienta de canelo) or Foye pepper, which can be used as a spice. The chemical and biological analysis of canelo fruits is reported for the first time in this study, that is, its phenolic fingerprinting by UHPLC-PDA- Q-orbitrap MS, the antioxidant activity, the enzymatic inhibitory activity, and its relaxation effects on rat aorta. The proximal composition and the mineral content (Ca: 1.45 ± 0.03 mg/100 g; Mg: 7.72 ± 0.03 mg/100 g; Fe: 4.54 ± 0.21 mg/100 g; Zn: 2.99 ± 0.02 mg/100 g; Mn: 1.08 ± 0.03 mg/100 g; Cu: 0.82 ± 0.02 mg/100 g; K: 53.03 ± 0.20 mg/100 g; Na: 0.087 ± 0.00 mg/100 g) are also reported. The canelo fruits showed a total phenolic content of 57.33 ± 0.82 mg GAE/g dry weight. In addition, the total flavonoid content was 38.42 ± 1.32 mg equivalent of QE/g dry weight. The antioxidant activity was evaluated by employing DPPH and ABTS methods (IC50 of 6.65 ± 0.5 and 9.5 ± 0.05 μg/mL, respectively), ORAC (25.33 ± 1.2 μmol Trolox/g dry plant) and FRAP (45.56 ± 1.32 μmol Trolox/g dry plant). The enzymatic inhibition of acetylcholinesterase, butyrylcholinesterase, and tyrosinase (IC50: 1.94 ± 0.07, 2.73 ± 0.05, and 9.92 ± 0.05 µg extract/mL, respectively) is also reported. Canelo extract led to an 89% relaxation of rat aorta. Our results confirm that D. winteri fruits are a rich source of secondary metabolites and can inhibit enzymes associated with neurodegenerative diseases; the results also suggest that canelo may induce a potentially hypotensive effect in rat aorta. The study demonstrates the medicinal properties of canelo fruit and spice. [ABSTRACT FROM AUTHOR]

Azara dentata Ruiz & Pav. is a small Chilean native plant from Patagonia, a producer of small white reddish berries. For the first time, the proximal analysis of the fruits, phenolic fingerprinting, the antioxidant activity, and the enzymatic inhibition and relaxation effects in rat aorta induced by the ethanolic extract of these fruits were investigated. The proximal composition and the mineral (Ca: 2434 ± 40 mg/kg; Mg: 702 ± 13 mg/kg; Fe: 117.1 ± 1.6 mg/kg; Zn: 16.1 ± 0.4 mg/kg) and heavy metal (As: 121 ± 11 µg/kg; Cd: 152 ± 5 µg/kg; Hg: 7.7 ± 1.3 µg/kg; Pb 294 ± 4 µg/kg) contents were analyzed. Anthocyanins, flavonoids, phenolic acids, and coumarins were identified using UHPLC-PDA-QTOF-MS. The ethanolic extracts showed a total phenolic content of 23.50 ± 0.93 mg GAE/g extract. In addition, the antioxidant activity was assessed using both DPPH and TEAC (28.64 ± 1.87 and 34.72 ± 2.33 mg Trolox/g of dry fruit, respectively), FRAP (25.32 ± 0.23 mg Trolox equivalent/g dry fruit), and ORAC (64.95 ± 1.23 mg Trolox equivalents/g dry fruit). The inhibition of enzymatic activities (acetylcholinesterase IC50: 2.87 + 0.23 µg extract/mL, butyrylcholinesterase IC50: 6.73 + 0.07 µg extract/mL, amylase IC50: 5.6 ± 0.0 µg extract/mL, lipase IC50: 30.8 ± 0.0 µg extract/mL, and tyrosinase IC50: 9.25 ± 0.15 µg extract/mL) was also assessed. The extract showed 50–60% relaxation in rat aorta (intact), mediated thorough the release of endothelial nitric oxide. Our results suggest that A. dentata is a good source of compounds with the capacity to inhibit important enzymes, can be hypotensive, and can thus have good potentiality as supplements in the amelioration of neurodegenerative diseases and could also have potential to be used to develop new functional foods. The study highlights the benefits of these neglected small fruits and could boost their consumption. [ABSTRACT FROM AUTHOR]

Gypothamnium pinifolium Phil. (Asteraceae) is a small shrub that grows in the Paposo Valley of the II Antofagasta Region of Chile. This initial study is of the high-resolution phenolic fingerprinting, antioxidant activity, the relaxation effects in rat aorta, the inhibitory enzyme potential, plus the antiproliferative activity of the ethyl acetate and n-hexane extract from G. pinifolium and its two major isolated secondary metabolites (one coumarin: 2-nor-1,2-secolycoserone, and one diterpene: ent-labda-8,13-E-diene-15-ol). The study involves using ultra-high-performance liquid chromatography todiode array detection coupled with Q-Orbitrap mass spectrometry analysis (UHPLC-PDA-Orbi-trap-MS), in which various compounds were identified, including specific coumarins. The n-hexane extract showed total phenolic and flavonoid contents of 517.4 ± 12.5 mg GAE/100 g extract and 72.3 ± 3.7 mg QE/100 g extract, respectively. In addition, the antioxidant activity of the n-hexane extract was assessed using in-vitro assays such as bleaching of DPPH and ABTS (IC50: 14.3 ± 0.52 and 2.51 ± 0.43 µg extract/mL, respectively), FRAP (347.12 ± 1.15 μmol Trolox equivalent/g extract), and ORAC (287.3 ± 1.54 μmol Trolox equivalents/g extract). Furthermore, the inhibition against cholinesterases (acetylcholinesterase (AChE) 4.58 ± 0.04 µg/mL, butyrylcholinesterase (BChE) IC50: 23.44 ± 0.03 µg/mL) and tyrosinase (IC50: 9.25 ± 0.15 µg/mL) enzymes of the n-hexane extract, and main compounds (IC50: 1.21 ± 0.03 µg/mL, 11.23 ± 0.02 µg/mL, 3.23 ± 0.12 µg/mL, and 103.43 ± 16.86 µg/mL, correspondingly for the most active coumarin 1) were measured. The antiproliferative potential of the extracts and the two principal compounds against several solid human cancer cells was investigated. All of them showed good activity against cancer cells. Label-free live-cell imaging studies on HeLa cells exposed to the isolated coumarin and the diterpene enabled the observation of cell death and several apoptotic hallmarks. Our results indicate that G. pinifolium Phil. is a valuable source of secondary metabolites with potential activity against noncommunicable diseases. [ABSTRACT FROM AUTHOR]

Senecio nutans Sch. Bip. and its constituents are reported to have antihypertensive effects. We isolated metabolite–1, a natural compound from S. nutans (4-hydroxy-3-(isopenten-2-yl)-acetophenone), and synthesized novel oxime – 1 (4-hydroxy-3-(isopenten-2-yl)-acetophenoxime) to evaluate their effect on vascular reactivity. Compounds were purified (metabolite–1) or synthetized (oxime–1) and characterized using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). Using pharmacological agents such as phenylephrine (PE) and KCl (enhancing contraction), acetylcholine (ACh), L-NAME (nitric oxide (NO) and endothelial function), Bay K8644-induced CaV1.2 channel (calcium channel modulator), and isolated aortic rings in an organ bath setup, the possible mechanisms of vascular action were determined. Pre-incubation of aortic rings with 10−5 M oxime–1 significantly (p < 0.001) decreased the contractile response to 30 mM KCl. EC50 to KCl significantly (p < 0.01) increased in the presence of oxime–1 (37.72 ± 2.10 mM) compared to that obtained under control conditions (22.37 ± 1.40 mM). Oxime–1 significantly reduced (p < 0.001) the contractile response to different concentrations of PE (10−7 to 10−5 M) by a mechanism that decreases Cav1.2-mediated Ca2+ influx from the extracellular space and reduces Ca2+ release from intracellular stores. At a submaximal concentration (10−5 M), oxime–1 caused a significant relaxation in rat aorta even without vascular endothelium or after pre-incubate the tissue with L-NAME. Oxime–1 decreases the contractile response to PE by blunting the release of Ca2+ from intracellular stores and blocking of Ca2+ influx by channels. Metabolite–1 reduces the contractile response to KCl, apparently by reducing the plasma membrane depolarization and Ca2+ influx from the extracellular space. These acetophenone derivates from S. nutans (metabolite–1 and oxime–1) cause vasorelaxation through pathways involving an increase of the endothelial NO generation or a higher bioavailability, further highlighting that structural modification of naturally occurring metabolites can enhance their intended pharmacological functions. [ABSTRACT FROM AUTHOR]

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Background: Xenophyllum poposum is an endemic species of the Andes Cordillera, popularly known as Popusa. Popusa is widely used by mountain communities as a folk medicine to treat altitude sickness and hypertension.Purpose: The aim of this study is to evaluate the hypotensive effects and vascular reactivity of Popusa extracts and its pure isolated compounds.Methods: Hydroalcoholic extract of Xenophyllum poposum (HAE X. poposum; 40 mg/kg dose) were administered to rats by gavage and mean arterial pressures were recorded. Organ bath studies were conducted in endothelium-intact and denuded rings, and the vascular reactivity of the HAE X. poposum extract and its isolated compounds were compared and analysed. Cytosolic Ca2+ was measured in vascular smooth muscle cell line A7r5 using Fura2-AM.Results: HAE X. poposum significantly reduced the mean arterial blood pressure and heart rate in normotensive rats chronically treated with the extract, as well as mice acutely treated with the extract. A negative chronotropic effect was observed in the isolated rat heart. HAE X. poposum induced endothelial vasodilation mediated by nitric oxide (NO), reduced the contractile response to PE, and decreased PE-induced intracellular Ca2+ influx in vascular smooth muscle cells. Pure compounds isolated from HAE X. poposum such as 4‑hydroxy‑3-(3-methyl-2-butenyl) acetophenone, 5-acetyl-6‑hydroxy‑2-isopropenyl-2, and 3-dihydrobenzofurane (dihydroeuparin) also triggered endothelium-dependent vasodilation.Conclusion: HAE X. poposum decreases blood pressure, heart rate and vascular response. The vasodilation properties of HAE X. poposum extract and its isolated compounds may act through the endothelial nitric oxide synthase, as well as calcium channel blocker mechanisms. The results of the present study provide the first qualitative analysis that supports the use of X. poposum in traditional folk medicine for the treatment of altitude sickness and hypertension. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Senecio nutans Sch. Bip. (Compositae) is an endemic plant of South America used in the management of acute mountain sickness in the Andean communities. Currently, the direct effects of hydroalcoholic extract from S. nutans on the cardiovascular system are unknown. The aim of this study was to determine the effects and mechanism of action of S. nutans on cardiovascular function in normotensive and Angiotensin II (1 μg/mL) hypertension mice models. Material and methods Blood pressure and ECG measurements were simultaneously carried out on the mice and rats. The isolated right atrium, papillary muscle of the left ventricle and isolated heart of rat were used to study the cardiac functions and mechanisms. Results S. nutans (40 mg/Kg) induced a 30% and 12% significant ( p <0.05) reduction of the mean arterial pressure (MAP) in normotensive and hypertensive mice respectively. This decrease was as a result of decrease in heart rate (HR) in normotensive (25%) and hypertensive model (31%). It also decreased the sinus rhythm in isolated right atrium of rat. Compared with Losartan, a known anti-hypertensive, S. nutans caused a dose-dependent negative inotropic effect (dP/dtmax) on Langendorff isolated heart system. While Losartan, decreased the MAP by 30% but had no effect on heart rate. The calcium blocker nifedipine had similar effects as S. nutans , decreasing the beat frequency of isolated right atrium and contractility of papillary muscle of the left ventricle of rat. Conclusion The results suggest an important clinical function in hypertension therapy, as S. nutans could decrease the blood pressure in hypertensive mice by decreasing the HR and contractility, leading to a reduction in myocardial oxygen demand. [ABSTRACT FROM AUTHOR]

The aim of this work is to determine whether consuming tap water containing arsenic (20 mg/L) alters oxidative stress levels in female rats and changes vascular response. Whereas nitric oxide produces complete relaxation, arsenic (7 months of exposure) impairs the acetylcholine-induced endothelial relaxation in the rat aorta compared with control rats. Arsenic exposure results in a marked elevation in reactive oxygen species in blood, and d-aminolevulinic acid dehydratase activity, which is a sensitive biomarker for arsenic toxicity and oxidative stress, is significantly decreased in erythrocytes from 7-month-old rats. Diastolic blood pressure increases significantly in 7-month-old arsenic-treated versus control rats. The percentage of change in peripheral resistance increases. The results indicate that chronic environmental exposure to low levels of arsenic alters the release of vasoactive substances, causes changes in oxidative stress, and increases blood pressure in female rats. [ABSTRACT FROM PUBLISHER]

Inhibition of the Na+–K+–2Cl− cotransporter (NKCC1) with bumetanide reduced contractile responses to phenylephrine (PE) in male rat aortas (129±4% of 60 mM KCl-induced contraction control vs 108±7% bumetanide; PE 10−5 M; P<0.01) but did not change equivalent responses in female rat aortas. Removal of the endothelium blunted the effect of NKCC1 inhibition on the response to PE (10−5 M) in males, whereas in denuded aorta from female rats, bumetanide reduced this response (162±5% control vs 146±3% bumetanide; P<0.05).NKCC1 basal activity did not show gender differences in intact aortic rings, but in the presence of PE, bumetanide-sensitive 86Rb+/K+ uptake increased more in male than female aortas (179±8 in males vs 158±5 nmol 86Rb+/K+ min−1 (g aorta)−1 in females; P<0.05). PE did not stimulate NKCC1 activity in denuded aorta from male rats. However, in female rats, PE increased NKCC1 activity similarly in both denuded (169±11 nmol 86Rb+/K+ min−1 (g aorta)−1) and intact aortas.Ovariectomy increased the bumetanide-sensitive 86Rb+/K+ uptake increase elicited by PE (223±17 nmol 86Rb+/K+ min−1 (g aorta)−1) and hormone replacement with 17β-estradiol prevented this effect (159±29 nmol 86Rb+/K+ min−1 (g aorta)−1).Na+,K+-ATPase basal activity, measured as ouabain-sensitive 86Rb+/K+ uptake, was similar in male and female rats, but the effect of PE was significantly less in intact male aortas (232±16 in males vs 296±25 nmol 86Rb+/K+ min−1 (g aorta)−1 in females; P<0.05).Our results suggest that PE induced activation of NKCC1 and Na+,K+-ATPase in the rat aorta in a gender-dependent way.British Journal of Pharmacology (2006) 148, 964–972. doi:10.1038/sj.bjp.0706818; published online 26 June 2006 [ABSTRACT FROM AUTHOR]

Mangifera indica Linn popularly known as mango is used in folk medicine to treat gastrointestinal disorders. The aim of this study was to identify the metabolomic composition of lyophilized extract of mango leaf (MIE), to evaluate the antioxidant activity on several oxidative stress systems (DPPH, FRAP, TBARS, and ABTS), the spasmolytic and antispasmodic activity, and intestinal protective effect on oxidative stress induced by H2O2 in rat ileum. Twenty-nine metabolites were identified and characterized based on their ultra-high-performance liquid chromatography (UHPLC) high-resolution orbitrap mass spectrometry, these include: benzophenone derivatives, xanthones, phenolic acids, fatty acids, flavonoids and procyanidins. Extract demonstrated a high antioxidant activity in in-vitro assays. MIE relaxed (p < 0.001) intestinal segments of rat pre-contracted with acetylcholine (ACh) (10−5 M). Pre-incubation of intestinal segments with 100 µg/mL MIE significantly reduced (p < 0.001) the contraction to H2O2. Similar effects were observed with mangiferin and quercetin (10−5 M; p < 0.05) but not for gallic acid. Chronic treatment of rats with MIE (50 mg/kg) for 28 days significantly reduced (p < 0.001) the H2O2-induced contractions. MIE exhibited a strong antioxidant activity, spasmolytic and antispasmodic activity, which could contribute to its use as an alternative for the management of several intestinal diseases related to oxidative stress. [ABSTRACT FROM AUTHOR]

Heliotropium taltalense is an endemic species of the northern coast of Chile and is used as folk medicine. The polyphenolic composition of the methanolic and aqueous extract of the endemic Chilean species was investigated using Ultrahigh-Performance Liquid Chromatography, Heated Electrospray Ionization and Mass Spectrometry (UHPLC-Orbitrap-HESI-MS). Fifty-three compounds were detected, mainly derivatives of benzoic acid, flavonoids, and some phenolic acids. Furthermore, five major compounds were isolated by column chromatography from the extract, including four flavonoids and one geranyl benzoic acid derivative, which showed vascular relaxation and were in part responsible for the activity of the extracts. Since aqueous extract of H. taltalense (83% ± 9%, 100 μg/mL) produced vascular relaxation through an endothelium-dependent mechanism in rat aorta, and the compounds rhamnocitrin (89% ± 7%; 10−4 M) and sakuranetin (80% ± 6%; 10−4 M) also caused vascular relaxation similar to the extracts of H. taltalense, these pure compounds are, to some extent, responsible for the vascular relaxation. [ABSTRACT FROM AUTHOR]

The infusion of the desertic plant Nolana ramosissima I.M. Johnst showed vascular smooth muscle relaxation in rat aorta and the presence of several phenolic compounds, which were detected by high resolution UHPLC-Orbitrap-HESI-MS. In addition, five flavonoids were rapidly isolated from a methanolic extract using high-performance counter-current chromatography (HPCCC). The N. ramosissima extract showed endothelium-independent relaxation effect in rat aorta. Sixty-one compounds were detected in the infusion, mainly glycosylated flavonoids, flavanones and several oxylipins, suggesting that a synergistic effect between the compounds in the extracts could be responsible for the relaxation activity. Vascular activity experiments were done in isolated organ bath. In rat aorta, a nitric oxide inhibitor did not prevent the relaxation effects of the extract; however, a selective guanylyl cyclase inhibitor partially blunted this effect. The compound 5,3′-dihydroxy-4′7-dimethoxyflavone presented higher relaxation effect than 100 μg/mL of N. ramosissima extract. The extract and the isolated metabolites from N. ramosissima can show relaxation effects on rat aorta by a mechanism that is independent of the endothelium. [ABSTRACT FROM AUTHOR]

Parastrephia quadrangularis (Pq), commonly called "Tola", is widely used in folk medicine in the Andes, including for altitude sickness. In this study, polyphenolic composition was determined, and hypotensive effects were measured; the ethnopharmacological use as hypotensive was related to the presence of phenolic compounds. For this purpose, male Sprague-Dawley rats (6 to 8 weeks of age, 160 to 190 g) were fed Pq extract (10 to 40 mg/kg) for 10 days through gavage. Blood pressures and heart rate were significantly (p < 0.01) reduced in normotensive rats receiving Pq extract (40 mg/kg body weight). Pq extract induced a negative inotropic effect, and endothelium-dependent vasodilation mediated by nitric oxide (NO). Furthermore, preincubation with Pq extract significantly decreased the cytosolic calcium on vascular smooth muscle cells A7r5 in response to L-phenylephrine (PE). Seven metabolites were isolated from the Pq extract, but three flavonoids (10−4 M) showed similar vasodilation to the extract in intact rat aorta as follows: 5,3′,4′-trihydroxy-7-methoxyflavanone (2); 3,5,4′-trihydroxy-7,8,3′-trimethoxyflavone (6); and 5,4′-dihydroxy-3,7,8,3′-tetramethoxyflavone (7). The Pq extract and compounds 2 and 7 significantly (p < 0.05) reduced the contraction to Bay K8644 (10 nM, an agonist of CaV1.2 channels). Administration of Pq decreased cardiac contractility and increased endothelium-dependent and -independent vasodilation. [ABSTRACT FROM AUTHOR]

Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. Aristotelia chilensis (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 μM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 μM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 μM BaCl2 (Kir), 10 μM glibenclamide (KATP), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (p < 0.05) reduced the ARI-induced relaxation. ARI significantly (p < 0.05) reduced the contractile response to agonist of CaV1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway. [ABSTRACT FROM AUTHOR]

Guinep is traditionally used in the management of cardiovascular ailments. This study aims to evaluate its medicinal constituents and effects in the management of myocardial injury in an experimental isoproterenol (ISO) rat model. Sprague-Dawley rats were randomly assigned to four groups: Group 1 was the control group; Group 2 received M. bijugatus extract (100 mg/Kg; MB) for six weeks; Group 3 was given ISO (85 mg/Kg) i.p. twice during a 24-hour period; and Group 4 was given ISO (85 mg/Kg) i.p. and MB extract (100 mg/Kg) for six weeks. The MB was administered orally by gavage, daily. The blood pressure of conscious animals was measured, while ECG was performed under anesthesia. Blood and serum were collected for biochemical and hematological analysis. The ISO group treated with MB showed a significant decrease (p < 0.001) in (SBP), diastolic (DBP), mean arterial (MAP) and heart rate (HR) compared to the ISO only group. Conversely, MB treated rats that were not induced with ISO displayed a significant decreases (p < 0.001) in SBP, DBP, MAP, and HR. ISO significantly elevated the ST segment (p < 0.001) and shortened the QTc interval (p < 0.05), which were recovered after treatment with 100 mg/Kg of MB. In addition, the results showed a significant decrease (p < 0.001) in the heart to body weight ratio of the ISO group treated with MB compared to the ISO only group. Furthermore, the extract normalized the hematological values depressed by the ISO while significantly elevating the platelet count. UHPLC high-resolution orbitrap mass spectrometry analysis results revealed the presence of several antioxidants like vitamin C and related compounds, phenolic acids, flavonoid, fatty acids (oxylipins), and terpene derivatives. The results of this study indicated that Melicoccus bijugatus did display some cardio-protective effects in relation to myocardial injury. [ABSTRACT FROM AUTHOR]

8-Oxo-9-dihydromakomakine is a tetracyclic indole alkaloid extracted from leaves of the Chilean tree Aristotelia chilensis. The present study investigated the effects of this alkaloid on vascular response in tissues isolated from aortic segments obtained from normotensive rats. Our results showed that 8-oxo-9-dihydromakomakine induced a dose-dependent relaxation of aortic rings pre-contracted with phenylephrine (PE; 10−6 M). The vasorelaxation induced by 8-oxo-9-dihydromakomakine in rat aortic rings is independent of endothelium. The pre-incubation of aortic rings with 8-oxo-9-dehydromakomakine (10−4 M) significantly reduced the contractile response to KCl (p < 0.001) more than PE (p < 0.05). The highest dose of 8-oxo-9-dehydromakomakine (10−4 M) drastically reduced the contraction to KCl (6·10−2 M), but after that, PE (10−6 M) caused contraction (p < 0.05) in the same aortic rings. The addition of 8-oxo-9-dihydromakomakine (10−5 M) decreased the contractile response to tetraethylammonium (a voltage-dependent potassium channels blocker; TEA; 5 × 10−3 M; p < 0.01) and BaCl2 (a non-selective inward rectifier potassium channel blocker; 5 × 10−3 M; p < 0.001) in rat aorta. 8-oxo-9-dihydromakomakine (10−5 M) decreased the contractile response to PE in rat aorta in the presence or absence of ouabain (an inhibitor of Na,K-ATPase; 10−3 M; p < 0.05). These results could indicate that 8-oxo-9-dihydromakomakine partially reduces plasma membrane depolarization-induced contraction. In aortic rings depolarized by PE, 8-oxo-9-dihydromakomakine inhibited the contraction induced by the influx of extracellular Ca2+ in a Ca2+ free solution (p < 0.01). 8-oxo-9-dihydromakomakine reduced the contractile response to agonists of voltage-dependent calcium channels type L (Bay K6844; 10−8 M; p < 0.01), likely decreasing the influx of extracellular Ca2+ through the voltage-dependent calcium channels. This study provides the first qualitative analysis indicating that traditional folk medicine Aristotelia chilensis may be protective in the treatment of cardiovascular pathologies. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats. Material and methods Twenty (20) adult male Sprague-Dawley rats (175–230 g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50 mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85 mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100 mg/Kg AA respectively for 6 days, after induced with ISO twice (85 mg/Kg) at a 24-h period. Blood pressure readings were taken before and after the administering of ISO using the tail cuff method. ECG was performed on anaesthetized rats. Cardiac contractility was measured in isolated right atrial muscles. Assessment of myocardial infarct (MI) size, heart/body weight ratio, biochemical, hematological and histo-morphological parameters were conducted at the end of seven days. An aqueous extract from leaves of A. altilis was analyzed for organic compounds using UHPLC mass spectrometry. Results ISO induced myocardial damage through an elevation of the heart rate (HR), infarct size and ECG distortions. Treatment with AA significantly (p˂0.05) reduced heart/body weight ratio (49%), MI (96%), HR (27%), sympathovagal imbalance (36%) and serum cardiac biomarkers (AST, LDH, HDL, triglycerides and CCK) caused by ISO. AA decreased the beat frequency of isolated right atrium (11%) cause by ISO, an action similar to propranolol (beta-adrenergic antagonist; 20%), but showed no significant changes in the QTc intervals of the ECG (suggesting no cardio-toxic drug-herb interactions), Thirty nine compounds were detected using high resolution LC-MS analysis (HPLC-Orbitrap-APCI-MS) in the extract. Pure compounds, as gallic acid and rutin, presented a higher negative chronotropic effect, similar to propranolol. Conclusion Oral administration of aqueous extract of Artocarpus artilis has cardio-protective functions in myocardial injury, in part, by decreasing the HR, reduced contractility and infarct size. These findings may explain the cardio-protective use of A. altilis in traditional medicine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Senecio nutans Sch. Bip. (Compositae) is an endemic plant of South America, and is used in herbal medicine in Andean communities for treating acute mountain sickness. Currently, the direct effects of hydroalcoholic extract of S. nutans (HAE S. nutans ) or its isolated compounds on the vascular system are not well described. The aim of this study was to determine the effects and mechanism of action of S. nutans on vascular function in healthy rats. Material and methods Seven compounds were isolated from the HAE S. nutans , and their structures were characterized using spectroscopic techniques as 1D and 2D NMR, and mass spectrometry. Vascular reactivity experiments were carried out in rat aorta. S. nutans -dependent vasodilation and phenylephrine-dependent contraction were measured in endothelium-intact and endothelium-denuded aortic rings of male rats. Results Seven pure compounds were isolate from HAE S. nutans , but two pure compounds showed significant vasodilation in rat aorta: 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone (compound E ) and 5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane (compound G ). Although HAE S. nutans induced vasodilation in absence of endothelium, the vasodilation in intact aorta, via NO, was higher. HAE S. nutans reduced calcium-dependent contraction in endothelium-intact, but not in endothelium-denuded aortic rings. Conclusion HAE S. nutans and its isolated compounds caused vasodilation in rat aorta in absence of endothelium, suggesting its vasodilator properties is endothelium-dependent (NO) and or independent, and may involve a modulation of the calcium channels. This result is of clinical interest as potential therapy control of blood pressure. [ABSTRACT FROM AUTHOR]