Abstract：
OBJECTIVE:The vasorelaxant effect of 2-arachidonoylglycerol (2-AG) has been well characterised in animals. 2-AG is present in human vascular cells and is up-regulated in cardiovascular pathophysiology. However, the acute vascular actions of 2-AG have not been explored in humans. APPROACH:Mesenteric arteries were obtained from patients receiving colorectal surgery and mounted on a myograph. Arteries were contracted and 2-AG concentration-response curves were carried out. Mechanisms of action were characterised pharmacologically. Post hoc analysis was carried out to assess the effects of cardiovascular disease/risk factors on 2-AG responses. RESULTS:2-AG caused vasorelaxation of human mesenteric arteries, independent of cannabinoid receptor or transient receptor potential vanilloid-1 activation, the endothelium, nitric oxide or metabolism via monoacyglycerol lipase or fatty acid amide hydrolase. 2-AG-induced vasorelaxation was reduced in the presence of indomethacin and flurbiprofen, suggesting a role for cyclooxygenase metabolism 2-AG. Responses to 2-AG were also reduced in the presence of Cay10441, L-161982 and potentiated in the presence of AH6809, suggesting that metabolism of 2-AG produces both vasorelaxant and vasoconstrictor prostanoids. Finally, 2-AG-induced vasorelaxation was dependent on potassium efflux and the presence of extracellular calcium. CONCLUSIONS:We have shown for the first time that 2-AG causes vasorelaxation of human mesenteric arteries. Vasorelaxation is dependent on COX metabolism, activation of prostanoid receptors (EP4 & IP) and ion channel modulation. 2-AG responses are blunted in patients with cardiovascular risk factors.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Stanley CP,O'Sullivan SEdoi
10.1016/j.phrs.2014.02.001subject
Has Abstractpub_date
2014-03-01 00:00:00pages
74-82eissn
1043-6618issn
1096-1186pii
S1043-6618(14)00014-0journal_volume
81pub_type
杂志文章abstract：:Mammals and their intestinal microbiota peacefully coexist in a mutualistic relationship. Commensal bacteria play an active role in shaping and modulating physiological processes in the host, which include, but are not restricted to, the immune system and the intestinal barrier. Both play a crucial role in containing ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2012.10.007
更新日期：2013-03-01 00:00:00
abstract：:Endocannabinoids are part of a bioactive lipid signaling system, not only in the central nervous system but also in various peripheral organs. Accumulating evidence implicates dysregulation of the endocannabinoid system (ECS) in the pathogenesis of various cardiovascular diseases, including hypertension, atheroscleros...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2009.04.003
更新日期：2009-08-01 00:00:00
abstract：:Potential risks of cyclohexanol (CH) and cyclohexanediol (CHD) isomers, which are the metabolites derived from cilexetil ester side-chain of several prodrugs such as antibiotics (e.g. cefotiam hexetil) and an antihypertensive agent (candesartan cilexetil), were examined in beagles that were made congestive heart failu...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043661802001743
更新日期：2002-10-01 00:00:00
abstract：:Flt3 is expressed by early myeloid and lymphoid progenitor cells and it regulates the proliferation and differentiation of hematopoietic cells. Flt3 is activated by the Flt3 ligand, the monomeric form of which is a polypeptide of about 200 amino acid residues. Both membrane-associated and soluble Flt3 ligands, which a...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104725
更新日期：2020-05-01 00:00:00
abstract：:Cysteamine, a potent somatostatin depletor, was used in the present study to investigate the role of endogenous somatostatin in acute peripheral inflammation. The acute inflammation was induced by intraplantar injection of carrageenan (1%), histamine (5 micromol), or formalin (2.5%) in the rat hind paw. The induced in...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2002.0955
更新日期：2002-04-01 00:00:00
abstract：:The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by re...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2013.05.003
更新日期：2013-08-01 00:00:00
abstract：:The Renin Angiotensin System (RAS) is a pivotal physiological regulator of heart and kidney homeostasis, but also plays an important role in the pathophysiology of heart and kidney diseases. Recently, new components of the RAS have been discovered, including angiotensin converting enzyme 2 (ACE2), Angiotensin(Ang)-(1-...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2016.03.018
更新日期：2016-05-01 00:00:00
abstract：:Erdosteine was introduced in the market as a mucolytic agent for chronic pulmonary diseases more than 10 years ago. The drug contains two blocked sulphydryl groups one of which, after hepatic metabolization and opening of the thiolactone ring, becomes available both for the mucolytic and free radical scavenging and an...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2006.12.006
更新日期：2007-04-01 00:00:00
abstract：:Indole-based compounds, such as the alkyl-indole (AI) compound WIN55212-2, activate the cannabinoid receptors, CB1 and CB2, two well-characterized G protein-coupled receptors (GPCR). Reports indicate that several indole-based cannabinoid agonists, including WIN55212-2, lack selectivity and interact with at least two a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.10.025
更新日期：2017-01-01 00:00:00
abstract：:Nephrotoxicity associated with cyclosporine A (CsA) administration is characterized by marked renal vasoconstriction, interstitial fibrosis and arteriolar hypertrophy. The molecular mechanisms of CsA nephrotoxicity are not well characterized, but previous studies have demonstrated that angiotensin II (Ang II), the pri...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2002.0959
更新日期：2002-05-01 00:00:00
abstract：:Short-chain fatty acids (SCFAs), mainly including acetate, propionate, and butyrate, are metabolites produced during the bacterial fermentation of dietary fiber in the intestinal tract. They are believed to be essential factors affecting host health. Most in vitro and ex vivo studies have shown that SCFAs affect the r...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2021.105420
更新日期：2021-01-09 00:00:00
abstract：:The endogenous gasotransmitter hydrogen sulphide (H2S) is an important regulator of the cardiovascular system, particularly of myocardial function. Moreover, H2S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury, and is considered an important mediator of "ischemic preconditioning...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.09.006
更新日期：2016-11-01 00:00:00
abstract：:Bleomycin (BLM) is a drug used to treat different types of neoplasms. BLM's most severe adverse effect is lung toxicity, which induces remodeling of lung architecture and loss of pulmonary function, rapidly leading to death. While its clinical role as an anticancer agent is limited, its use in experimental settings is...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2015.04.012
更新日期：2015-07-01 00:00:00
abstract：:The DNA microarrays have proven to be a state of the art technique for high throughput comprehensive analysis of thousand of genes in parallel. The application of a DNA microarray to compare normal and pathological cells, tissues or organs may allow, along with classical positional cloning techniques, to speed up the ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2003.06.001
更新日期：2004-04-01 00:00:00
abstract：:Pharmacokinetic of methyldopa (50 mg kg(-1)i.p.) was studied in anesthetized sham operated and sinoaortic denervated (SAD) rats by using the microdialysis technique. Vascular shunt probe was inserted into the carotid artery and concentric probe was placed in the striatum. Levels of methyldopa were measured by HPLC-EC....
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1999.0610
更新日期：2000-04-01 00:00:00
abstract：:Antifertility activity of a triterpenoid glycoside, DSS, isolated from the root of Dalbergia saxatilis was investigated in female Wistar rats of breeding age. When administered by gastric intubation at a dose rate of 200 mg kg(-1)body weight at the premating period, conception was inhibited in 71.4% of the treated ani...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1999.0615
更新日期：2000-05-01 00:00:00
abstract：:The human gut is populated by an array of bacterial species, which develop important metabolic and immune functions, with a marked effect on the nutritional and health status of the host. Dietary component also play beneficial roles beyond basic nutrition, leading to the development of the functional food concept and ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2009.11.001
更新日期：2010-03-01 00:00:00
abstract：:Biosimilars started receiving the marketing authorization by European Medicine Agency since 2006. The development of biosimilars follows a well-defined step-wise approach, the so-called comparability exercise, which aims to compare non-clinical (mainly quality features and biological activity) and clinical (efficacy a...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.11.002
更新日期：2017-12-01 00:00:00
abstract：:It is generally accepted that divalent cations are involved in the nociceptive pathway. The effect of systemic co-administration of magnesium sulfate and calcium channel blockers (nifedipine, verapamil) on the analgesic effect of opioid (mixed mu/kappa: butorphanol) and non-opioid drugs (paracetamol) was investigated....
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2001.0811
更新日期：2001-06-01 00:00:00
abstract：:The renal and metabolic effects of chronic carnitine administration were evaluated in the early stages of experimentally-induced renal failure. Laevo-carnitine (n = 5), Propionyl-carnitine (n = 5) both at 200 mg kg-1 of body weight, or vehicle (physiological saline solution, 0.4 ml kg-1 body weight, n = 5) were admini...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0083
更新日期：1996-09-01 00:00:00
abstract：:Derivatization of phenothiazine (PTZ, 1) has been a commonly used method to develop drugs with various pharmacological properties. In the present study, a series of PTZ derivatives 1-11 were investigated on the inhibition of the cloned α7 subunit of the human nicotinic acetylcholine receptor (α7-nAChR) expressed in Xe...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2012.05.008
更新日期：2012-09-01 00:00:00
abstract：:In this investigation we have examined the effects of indomethacin, an inhibitor of the cyclooxygenase pathway of arachidonic acid, upon the kinetics of the release of tumour necrosis factor alpha (TNF) and of the expression of TNF gene by lipopolysaccharide (LPS)-stimulated human blood monocytes (BM). Following stimu...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80084-2
更新日期：1991-04-01 00:00:00
abstract：:Cardiac arrhythmia can be a serious complication during general anaesthesia of patients suffering from cardiac arrhythmias and using antiarrhythmic drugs. The aim of the present experiments was to establish the way in which lidocaine and verapamil influence haemodynamic parameters of rabbits after midazolam anaesthesi...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1998.0464
更新日期：1999-06-01 00:00:00
abstract：:Epidemiological, clinical and animal studies revealed that sex differences exist in the manifestation and outcome of cardiovascular disease (CVD). The underlying molecular mechanisms implicated in these sex differences are not fully understood. The reasons for sex differences in CVD are definitely multifactorial, but ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.01.019
更新日期：2017-05-01 00:00:00
abstract：:Recent studies clearly show that there is a relationship between endotoxemia and impaired vascular responsiveness. The aim of this study was to investigate whether treatment with the new potent PARP inhibitor PJ34 could prevent the vascular hyporesponsiveness induced by lipopolysaccharide (LPS). Endotoxemia was induce...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2005.02.020
更新日期：2005-06-01 00:00:00
abstract：:We have previously reported that the dopaminergic projection from A10 ventral tegmental neurons to the central amygdala is, in part, responsible for the facilitatory effect of angiotensin II (AII) and its 3-7 fragment [AII(3-7)] on the retrieval of information in memory motivated affectively and also on recognition me...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0257
更新日期：1997-11-01 00:00:00
abstract：:The first studies of histamine and diabetes date back to the 1950s. Since that time the involvement of histamine in diabetes was related to its well known vasoactive properties and permeability leakage effects. In particular, the first evidence for a correlation between histamine and diabetes arose in 1989 when an inc...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2016.06.021
更新日期：2016-09-01 00:00:00
abstract：:The protective effect of L-carnitine or coenzyme Q10 (CoQ10) against high magnetic field (20 mT) induced testicular toxicity in mice were evaluated. Animals were injected with L-carnitine (200 mg kg(-1), i.p.) or CoQ10 (200 mg kg(-1), p.o.) 1h before exposure to fractionated doses (30 min per day, three times per week...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043661802001718
更新日期：2002-10-01 00:00:00
abstract：:The pharmacokinetics of doxycycline hydrochloride (DoxHcl) at a dose of 5 mg kg-1 BW was studied after an intravenous (i.v.) bolus and intramuscular (i.m.) injections in non lactating goats. A microbiological assay employing Bacillus subtilis as the test organism was used to measure its concentrations in serum and uri...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2003.10.012
更新日期：2004-05-01 00:00:00
abstract：:A major focus of contemporary drug screening strategies is the identification of novel anticancer compounds, which often results in underutilization of resources. Current drug evaluation involves in vivo tumor (xenograft) regression as proof-of-principle for cytotoxicity (POC). However, this end-point lacks any assess...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.07.018
更新日期：2016-09-01 00:00:00
