A systematic review of mechanisms by which natural products of plant origin evoke vasodilatation

2006 ◽  
Vol 84 (8-9) ◽  
pp. 803-821 ◽  
Author(s):  
J. Robert McNeill ◽  
Tannis M. Jurgens
Keyword(s):  
Nitric Oxide ◽  
Natural Products ◽  
Potassium Channel ◽  
Mechanisms Of Action ◽  
Oxide System ◽  
The Body ◽  
Plant Origin ◽  
Nitric Oxide Synthase Inhibitor ◽  
Channel Function

This article reviews the body of work aimed at elucidating the mechanisms of action by which natural products of plant origin exert a vasodilatory effect at the level of the vasculature. The search was restricted to 4 mechanisms: the nitric oxide system and (or) reactive oxygen species, the eicosanoid system, potassium channel function, and calcium channel function. The National Library of Medicine database was searched using “PubMed” without restriction to language. The search generated 266 references on 15 November 2005. Most studies were in vitro in nature and of these, most involved studies in the rat aorta. Many of the natural products evoked vasodilatation through an endothelium-dependent mechanism. The vasodilatation was attenuated or abolished by a nitric oxide synthase inhibitor and, in some of these studies, by an inhibitor of guanylate cyclase. A few studies reported a cyclooxygenase component, but most found no effect of the cyclooxygenase inhibitor, indomethacin. The vasorelaxation evoked by several natural products was attenuated by various potassium channel blocking agents, suggesting that some natural products exerted their effect either directly or indirectly through activation of potassium channels. Finally, a significant number of natural products evoked vasodilatation either through blockade of calcium channels or by inhibiting the release of calcium from intracellular stores. Many natural products evoked vasodilatation through multiple mechanisms. The information in this review on mechanisms of action should facilitate good clinical practice by increasing the predictive capabilities of the practitioner, notably the ability to predict adverse effects and interactions among medications. The knowledge should also help to provide leads to the ultimate goal of developing new therapeutic medications.

scholarly journals Coupled Nitric Oxide and Autonomic Receptor Functional Responses in the Normal and Inflamed Urinary Bladder of the Rat

2012 ◽  
pp. 371-380 ◽  
Author(s):  
R. VESELÁ ◽  
H. ASKLUND ◽  
P. ARONSSON ◽  
M. JOHNSSON ◽  
V. WSOL ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Urinary Bladder ◽  
The Body ◽  
Bladder Function ◽  
Detrusor Muscle ◽  
Functional Responses ◽  
Nitric Oxide Synthase Inhibitor ◽  
Parasympathetic Nerve ◽  
Contractile Responses

Both divisions of the autonomic nervous system are involved in regulation of urinary bladder function. Several substances, other than noradrenaline and acetylcholine, seem to play important roles in physiology and pathophysiology of lower urinary tract. In the current study, we aimed to examine if there exist interplays between nitric oxide (NO) and autonomic transmitters and if such interactions vary in different parts of the urinary bladder in healthy and cyclophosphamide (CYP)-induced cystitic rats; when administered to the animals (100 mg/kg; i.p.), the cytotoxic CYP metabolite acrolein induces bladder inflammation. In the current study a series of in vitro functional studies were performed on detrusor muscle strip preparations. Stimulation with electrical field stimulation (EFS), methacholine, adenosine 5´-triphosphate (ATP), and adrenaline evoked contractile responses in isolated bladder preparations that were significantly reduced in cyclophosphamide (CYP)-treated rats. While the nitric oxide synthase inhibitor Nω nitro-L-arginine (L-NNA; 10-4 M) did not affect contractile responses in normal, healthy strip preparations, it significantly increased the contractile responses to EFS, methacholine and adrenaline, but not to ATP, in the bladders from the CYP-treated rats. In the CYP-treated rats, the ATP-evoked relaxatory part of its dual response (an initial contraction followed by a relaxation) was 6-fold increased in comparison with that of normal preparations, whereas the isoprenaline relaxation was halved in the CYP-treated. While L-NNA (10-4 M) had no effect on the isoprenaline-evoked relaxations, it reduced the ATP-evoked relaxations in strip preparations from the bladder body of CYP-treated rats. Stimulation of β2- and β3 adrenoceptors evoked relaxations and both responses were reduced in cystitis, the latter to a larger extent. In the trigone, the reduced ATP-evoked contractile response in the inflamed strips was increased by L-NNA, while L NNA had no effect on the ATP-evoked relaxations, neither on the relaxations in healthy nor on the larger relaxations in the inflamed trigone. The study shows that both contractile and relaxatory functions are altered in the state of inflammation. The parasympathetic nerve-mediated contractions of the body of the bladder, evoked by the release of ATP and acetylcholine, were substantially reduced in cystitis. The relaxations to β-adrenoceptor and purinoceptor stimulation were also reduced but only the ATP-evoked relaxation involved NO.

Abstract 18060: TRAIL Promotes Angiogenesis and Ischemia-Induced Neovascularisation via NOX4, H2O2 and Nitric Oxide-Dependent Mechanisms

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Belinda A Di Bartolo ◽  
Sian P Cartland ◽  
Leonel Prado-Lourenco ◽  
Nor Saadah M Azahri ◽  
Thuan Thai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiogenic Factor ◽  
Tubule Formation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Therapeutic Implications ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
First Time

Background: Angiogenesis and neovascularization are essential processes that follow ischemia insults. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) not only induces endothelial cell (EC) death and inhibits angiogenesis, but also promotes EC migration, invasion and proliferation in vitro . These seemingly opposite effects make its role in angiogenesis in vivo unclear. Using TRAIL -/- and wild-type mice, we sought to determine the role of TRAIL in angiogenesis and neovascularisation. We also sought mechanisms in vitro . Methods and Results: Reduced vascularisation assessed by real-time in vivo 3D Vevo ultrasound imaging and CD31 staining was observed in TRAIL -/- mice 28 d after hindlimb ischemia. Moreover, reduced capillary formation and increased apoptosis was evident in TRAIL -/- muscles even at 3 d after ischemic surgery. We have previously shown that fibroblast growth factor-2 (FGF-2), a potent angiogenic factor, regulates TRAIL gene expression in vascular smooth muscle cells. Indeed, FGF-2 also regulates TRAIL expression in ECs, and FGF-2-inducible proliferation, migration and tubule formation was inhibited with siRNA targeting TRAIL. Notably, both FGF-2 and TRAIL significantly increased NOX4 expression. TRAIL-inducible angiogenic activity in ECs was inhibited with siRNAs targeting NOX4, and consistent with these, NOX4 mRNA was reduced in 3 d ischemic hindlimbs of TRAIL -/- mice. TRAIL stimulated intracellular H 2 O 2 levels in ECs, and TRAIL-inducible proliferation, migration and tubule formation was inhibited with not only PEG-catalase, a H 2 O 2 scavenger, but also blocked with L-NAME, a nitric oxide synthase inhibitor. Conclusions: This is the first demonstration showing that TRAIL promotes angiogenesis in vivo . We show for the first time that the TRAIL stimulates NOX4 expression to mediate nitric oxide-dependent angiogenic effects. This has significant therapeutic implications such that TRAIL may improve the angiogenic response to ischemia and increase perfusion recovery in patients with CVD and diabetes.

scholarly journals Natural products with therapeutic potential in melanoma metastasis

2015 ◽  
Vol 32 (8) ◽  
pp. 1170-1182 ◽  
Author(s):  
A. AlQathama ◽  
J. M. Prieto
Keyword(s):  
Natural Products ◽  
Cancer Treatment ◽  
Therapeutic Potential ◽  
Melanoma Cells ◽  
Mechanisms Of Action ◽  
Melanoma Metastasis ◽  
Pharmacological Effects ◽  
Cytotoxic Compounds

Natural products continue to provide lead cytotoxic compounds for cancer treatment but less attention has been given to antimigratory compounds. We here systematically and critically survey more than 30 natural products with direct in vitro and in vivo pharmacological effects on migration and/or metastasis of melanoma cells and chart the mechanisms of action for this underexploited property.

253 OXIDATIVE STRESS MAY IMPAIR OOCYTE QUALITY IN DAIRY COWS OF REPRODUCTIVE AGE WITH A REDUCED ANTRAL FOLLICLE COUNT

2013 ◽  
Vol 25 (1) ◽  
pp. 274 ◽  
Author(s):  
I. Tessaro ◽  
F. Franciosi ◽  
V. Lodde ◽  
D. Corbani ◽  
A. M. Luciano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Antral Follicle ◽  
Oocyte Quality ◽  
Antral Follicle Count ◽  
Oxide System ◽  
Reproductive Age ◽  
Developmental Competence ◽  
Mitochondrial Activity

In dairy cattle, oocytes isolated from ovaries with a reduced antral follicle count (AFC) have a low embryonic developmental competence. This may be related to oxidative stress, as indicated by our recent finding that ovaries with reduced AFC show a defective endothelial nitric oxide synthase/nitric oxide system. To further test this hypothesis, we evaluated whether the poor developmental competence of these oocytes was possibly due 1) to an imbalance of the reduced glutathione (GSH) system, because GSH is the major antioxidant compound stored within the oocyte and protects the zygote and early embryos from oxidative damage, and 2) to reduced mitochondrial activity. Ovaries were obtained from the abattoir, and oocytes were collected from ovaries with reduced AFC, with fewer than 10 follicles of 2 to 6 mm in diameter, and aged-matched controls, with more than 10 follicles of 2 to 6 mm in diameter. Oocyte GSH content was evaluated using the 5,5′-dithio-bis(2-nitrobenzoic acid)-GSH reductase recycling micro-GSH assay before and after in vitro maturation (IVM) in the presence or absence of 100 µM cysteamine, a GSH precursor. At the same time the developmental competence after IVF was assessed. Moreover, the mitochondrial activity during IVM was evaluated in additional oocytes from the two ovarian categories by specific MitoTracker dyes (MitoTracker FM Green and MitoTracker Orange CMTMRos, Invitrogen, Carlsbad, CA, USA) and subsequent image analysis (ImageJ software). All data were analysed by ANOVA followed by Fisher’s least significant differences test, and P-values <0.05 were considered significant. Experiments were repeated at least three times. Oocytes isolated from ovaries with a low AFC had a similar GSH content compared with oocytes isolated from control ovaries (n = 65 and 85, respectively; 4.31 ± 0.41 v. 4.51 ± 0.42 pmol oocyte–1). After IVM, oocytes from ovaries with reduced AFC showed a significantly lower GSH content compared with control oocytes (n = 55 and 65, respectively; 4.36 ± 0.31 v. 6.59 ± 0.39 pmol oocyte–1); however, cysteamine supplementation during IVM induced GSH accumulation similar to the control (n = 80 and 85, respectively; 9.88 ± 0.77 v. 10.45 ± 0.88 pmol oocyte–1). It is interesting that the increase in intracellular GSH content significantly improved the developmental competence of oocytes from ovaries with a reduced AFC (n = 196 and 201, respectively; 20.1 ± 2.9% v. 6.2 ± 1.6%), although the blastocyst rate remained lower than the control either with or without cysteamine (n = 218 and 212, respectively; 33.3 ± 3.8% and 34.2 ± 2.4%). Further, immature oocytes from ovaries with a low AFC showed a reduced mitochondrial membrane potential compared with control oocytes (n = 13 and 18, respectively; 1.74 ± 1.19 v. 2.22 ± 1.72, calculated as the ratio between the fluorescence of active and total mitochondria), whereas at the end of IVM, it declined in both categories at a comparable level (n = 17 and 24, respectively; 1.19 ± 0.10 and 1.30 ± 0.06). Our data confirmed the hypothesis that both the GSH imbalance and defective mitochondrial activity contribute to the limited developmental competence of oocytes from ovaries with a reduced AFC. This work was supported by Dote ricerca applicata-FSE, Regione Lombardia, Italy (VL, IT).

201 ROLE OF THE NITRIC OXIDE SYSTEM IN EFFECTS OF PROLACTIN AND GROWTH HORMONE ON METAPHASE-II CHROMOSOMES IN BOVINE OOCYTES AGING IN VITRO

2016 ◽  
Vol 28 (2) ◽  
pp. 231
Author(s):  
I. Lebedeva ◽  
G. Singina ◽  
E. Shedova ◽  
A. Lopukhov ◽  
N. Zinovieva
Keyword(s):  
Nitric Oxide ◽  
Growth Hormone ◽  
Cumulus Cells ◽  
Total Activity ◽  
Inhibitory Effect ◽  
Pituitary Hormones ◽  
Oxide System ◽  
Nos Inhibitors ◽  
Bovine Oocytes

Aging of mammalian oocytes is the time-dependent process of cytological and molecular transformations leading to a decline in the ovum quality and developmental capacity. We have previously shown that 2 related pituitary hormones, prolactin (PRL) and growth hormone (GH), may decelerate abnormal changes in the morphology of metaphase II (MII) chromosomes in bovine cumulus-enclosed oocytes (CEO) aging in vitro. The goal of the present research was to examine the involvement of different isoforms of nitric oxide synthase (NOS) in the actions of PRL and GH on MII chromosomes in aging bovine oocytes. Bovine CEO were matured for 20 h in TCM 199 containing 10% FCS, 10 μg mL–1 porcine FSH, and 10 μg mL–1 ovine LH. After IVM, CEO or denuded oocytes (DO) were cultured for 24 h in the aging medium of TCM 199 supplemented with 10% FCS (control). In experimental groups, the medium contained either 50 ng mL–1 bovine PRL or 10 ng mL–1 bovine GH and/or NOS inhibitors. The following inhibitors were applied: (1) N-propyl-l-arginine (NPLA; an inhibitor of neuronal NOS (nNOS), 5 μM) and (2) L-NAME (an effective inhibitor of both endothelial NOS (eNOS) and nNOS, 20 μM). Destructive changes of MII chromosomes in oocytes were assessed by the following morphological signs: decondensation, partial adherence, chromosome clumping into a single mass, and fragmentation. The total activity of NOS in oocytes was determined by NADPH-diaphorase staining. The data from 4–5 replicates were analysed by ANOVA. During CEO aging in the control medium, the rate of MII oocytes with destructive changes of chromosomes rose from 16.8 ± 2.1% to 58.5 ± 1.4% (P < 0.001), whereas both PRL and GH reduced this rate up to 42.0 ± 1.3% and 46.5 ± 1.6%, respectively (P < 0.001). The nNOS inhibitor NPLA abolished (P < 0.001) the inhibitory effect of PRL on abnormal modifications of chromosomes in CEO but did not affect the frequency of these modifications in the control or GH-treated groups. In the absence of the hormones, L-NAME (the eNOS+nNOS inhibitor) decreased the rate of aging CEOs with chromosome abnormalities from 58.5 ± 1.4% to 41.2 ± 2.5% (P < 0.001), acting unidirectionally with PRL and GH. Meanwhile, L-NAME enhanced (P < 0.05) the suppressing effect of PRL on destructive changes of MII chromosomes but did not influence the similar effect of GH. At the same time the chromosome morphology in senescent DOs was unaffected by the hormones or NOS inhibitors. Furthermore, the total activity of NOS in oocytes separated of cumulus after 24 h of aging was similar in the control and experimental groups. Thus, the inhibitory effect of GH on abnormal modifications of MII chromosomes in aging bovine oocytes may be related to a reduction of the eNOS activity in cumulus cells, whereas the respective effect of PRL is likely to be achieved by both inactivation of eNOS and activation of nNOS. This research was supported by RFBR (No. 13–04–01888).

Viral respiratory infection increases alveolar macrophage cytoplasmic motility in rats: role of NO

1995 ◽  
Vol 268 (3) ◽  
pp. L399-L406 ◽  
Author(s):  
T. Fukushima ◽  
K. Sekizawa ◽  
M. Yamaya ◽  
S. Okinaga ◽  
M. Satoh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Viral Infection ◽  
Respiratory Infection ◽  
Sendai Virus ◽  
The Body ◽  
Particle Rotation ◽  
Nitrite Production ◽  
Viral Respiratory Infection ◽  
Viral Respiratory

Ingested ferrimagnetic (Fe3O4) particles were used to estimate noninvasively the motion of organelles in alveolar macrophages (AM) in intact rats during viral respiratory infection by parainfluenza type 1 (Sendai) virus. Four days after instillation of Fe3O4 particles (3 mg/kg) into the lung, remnant field strength (RFS) was measured at the body surface immediately after magnetization of Fe3O4 particles by an externally applied magnetic field. RFS decreases with time, due to particle rotation (relaxation) which is related to cytoplasmic motility of AM. Viral infection increased the relaxation rate (lambda o per min), and increases in lambda o reached a maximum 3 days after nasal inoculation (day 3). Viral infection (day 3)-induced increases in lambda o were dose dependently inhibited by either the L-arginine analogue N-nitro-L-arginine or by methylene blue, an inhibitor of guanylate cyclase activity. Bronchoalveolar lavage fluid obtained from infected rats contained significantly higher levels of nitrite than that from control rats (P < 0.01). In in vitro experiments, AM from infected rats showed significantly higher lambda o, nitrite production, and intracellular guanosine 3',5'-cyclic monophosphate levels than those from control rats (P < 0.01). Sodium nitroprusside, known to release nitric oxide concentration dependently, increased lambda o of AM from noninfected rats in vitro. These results suggest that nitric oxide plays an important role in AM cytoplasmic motility during viral respiratory infection.

scholarly journals Cardiac mitochondrial ATP-sensitive potassium channel is activated by nitric oxide in vitro

FEBS Letters ◽  
2007 ◽  
Vol 581 (22) ◽  
pp. 4255-4259 ◽  
Author(s):  
Marko Ljubkovic ◽  
Yang Shi ◽  
Qunli Cheng ◽  
Zeljko Bosnjak ◽  
Ming Tao Jiang
Keyword(s):  
Nitric Oxide ◽  
Potassium Channel

Hypoxia Potentiates LPS-Mediated Cytotoxicity of BV2 Microglial Cells In Vitro by Synergistic Effects on Glial Cytokine and Nitric Oxide System

2015 ◽  
Vol 46 (05) ◽  
pp. 321-328 ◽  
Author(s):  
Florian Brackmann ◽  
Mandy Richter-Kraus ◽  
Regina Trollmann ◽  
Daniel Frey ◽  
Susan Jung
Keyword(s):  
Nitric Oxide ◽  
Synergistic Effects ◽  
Oxide System ◽  
Microglial Cells ◽  
Bv2 Microglial Cells ◽  
Nitric Oxide System

scholarly journals GABAergic Regulation of Cerebral Microvascular Tone in the Rat

1997 ◽  
Vol 17 (9) ◽  
pp. 992-1003 ◽  
Author(s):  
Andrea Fergus ◽  
Kevin S. Lee
Keyword(s):  
Nitric Oxide ◽  
Receptor Agonist ◽  
Computer Assisted ◽  
Local Concentration ◽  
Nitric Oxide Synthase Inhibitor ◽  
Cerebral Microvessels ◽  
Endogenous Gaba ◽  
Synthase Inhibitor ◽  
The Brain

The role of GABA in regulating cerebral microvessels was examined in the parenchyma of the hippocampus and the surface of the neocortex. Microvessels were monitored in in vitro slices using computer-assisted videomicroscopy, and synaptically evoked field responses were simultaneously recorded. γ-Aminobutyric acid (GABA) and the GABAA receptor agonist, muscimol, elicited vasodilation in hippocampal microvessels, whereas the GABAB receptor agonist, baclofen, elicited constriction. The muscimol-induced dilation persisted in the presence of the nitric oxide synthase inhibitor, N-nitro-l-arginine, indicating that this response is not mediated by nitric oxide. Inhibition of neuronal discharge activity with tetrodotoxin did not alter this dilation, but it fully blocked the constrictor response to baclofen. These data suggest that GABAB-mediated, but not GABAA-mediated, responses are dependent on action potential generation. The GABAA receptor antagonists, bicuculline and picrotoxin, elicited constriction, suggesting a tonic dilatory influence by endogenous GABA. Bicuculline-induced constriction was not attenuated by tetrodotoxin. In contrast, these vessels were unresponsive to the GABAB receptor antagonist, 2-hydroxysaclofen. Hippocampal microvessels dilated in response to moderate hypoxia, and this response persisted in the presence of bicuculline, indicating that the hypoxia-induced dilation is not mediated by an action at GABAA receptors. In arterioles located on the surface of the neocortex (i.e., not embedded in the parenchyma of the brain), muscimol elicited vasodilation, whereas bicuculline was ineffective. These results suggest that although these vessels are responsive to GABA, the local concentration of endogenous GABA is insufficient to elicit a tonic effect at rest. These findings raise the possibility that GABA plays a role in local neurovascular signaling in the parenchyma of the brain.

Endothelium-derived microparticles impair endothelial function in vitro

2004 ◽  
Vol 286 (5) ◽  
pp. H1910-H1915 ◽  
Author(s):  
Sergey V. Brodsky ◽  
Fan Zhang ◽  
Alberto Nasjletti ◽  
Michael S. Goligorsky
Keyword(s):  
Nitric Oxide ◽  
Surrogate Marker ◽  
Common Denominator ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Endothelial Microparticles ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor

Endothelial cell dysfunction (ECD) is emerging as the common denominator for diverse and highly prevalent cardiovascular diseases. Recently, an increased number of procoagulant circulating endothelial microparticles (EMPs) has been identified in patients with acute myocardial ischemia, preeclampsia, and diabetes, which suggests that these particles represent a surrogate marker of ECD. Our previous studies showed procoagulant potential of endothelial microparticles and mobilization of microparticles by PAI-1. The aim of this study was to test the effects of isolated EMPs on the vascular endothelium. EMPs impaired ACh-induced vasorelaxation and nitric oxide production by aortic rings obtained from Sprague-Dawley rats in a concentration-dependent manner. This effect was accompanied by increased superoxide production by aortic rings and cultured endothelial cells that were coincubated with EMPs and was inhibited by a SOD mimetic and blunted by an endothelial nitric oxide synthase inhibitor. Superoxide was also produced by isolated EMP. In addition, p22(phox) subunit of NADPH-oxidase was detected in EMP. Our data strongly suggest that circulating EMPs directly affect the endothelium and thus not only act as a marker for ECD but also aggravate preexisting ECD.

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