Abstract:
:1. The role of smooth muscle-derived lipoprotein lipase (LPL) that translocates to the endothelium surface on vascular dysfunction during atherogenesis is unclear. Thus, the role of vascular LPL on blood vessel reactivity was assessed in transgenic mice that specifically express human LPL in the circulatory system. 2. Aortic free fatty acids (FFAs) were increased by 69% in the transgenic mice expressing human LPL in aortic smooth muscle cells (L2LPL) compared with their non-transgenic littermates (L2). 3. Contractility to KCl was increased by 33% in aortae of L2LPL mice. Maximal contraction to phenylephrine (PE) was comparable in L2 and L2LPL animals, while the frequency of tonus oscillation to PE increased by 104% in L2LPL mice. 4. In L2LPL animals, *NO mediated relaxation to acetylcholine (ACh) and ATP was reduced by 47 and 32%, respectively. In contrast, endothelium-independent relaxation to sodium nitroprusside (SNP) was not different in both groups tested. 5. ATP-initiated Ca(2+) elevation that triggers *NO formation was increased by 41% in single aortic endothelial cells freshly isolated from L2LPL animals. 6. In aortae from L2LPL mice an increased *O(2)(-) release occurred that was normalized by removing the endothelium and by the NAD(P)H oxidase inhibitor DPI and the PKC inhibitor GF109203X. 7. The reduced ACh-induced relaxation in L2LPL animals was normalized in the presence of SOD, indicating that the reduced relaxation is due, at least in part, to enhanced *NO scavenging by *O(2)(-). 8. These data suggest that despite normal lipoprotein levels increased LPL-mediated FFAs loading initiates vascular dysfunction via PKC-mediated activation of endothelial NAD(P)H oxidase. Thus, vascular LPL activity might represent a primary risk factor for atherosclerosis independently from cholesterol/LDL levels.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Esenabhalu VE,Cerimagic M,Malli R,Osibow K,Levak-Frank S,Frieden M,Sattler W,Kostner GM,Zechner R,Graier WFdoi
10.1038/sj.bjp.0704440subject
Has Abstractpub_date
2002-01-01 00:00:00pages
143-54issue
1eissn
0007-1188issn
1476-5381journal_volume
135pub_type
杂志文章abstract::Ligands targeting GPCRs can be categorized according to their intrinsic efficacy to trigger a specific, receptor-mediated response. A ligand endowed with the same level of efficacy as the endogenous agonist can be classified as a full agonist, whereas a compound that displays greater efficacy, that is, higher receptor...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13278
更新日期:2016-10-01 00:00:00
abstract::Spontaneous inhibitory postsynaptic currents (i.p.s.cs) were recorded in voltage-clamped CA1 neurones in rat hippocampal slices. The exponential decay of i.p.s.cs was prolonged by concentrations of sodium pentobarbitone as low as 50 microM. With concentrations up to 100 microM, there was no change in the amplitude or ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb10563.x
更新日期:1985-07-01 00:00:00
abstract::The iodine-containing contrast medium iopanoic acid induces alterations of thyroid hormone metabolism comparable to those observed with the iodine-containing antiarrhythmic drug amiodarone. Both compounds inhibit the intracellular conversion of thyroxine (T4) to triiodothyronine (T3). Using iopanoic acid, the question...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10217.x
更新日期:1986-06-01 00:00:00
abstract::1. Pre-eclampsia is a serious pregnancy disorder associated with widespread activation of the maternal vascular endothelium. Recent evidence implicates a role for oxidative stress in the aetiology of this condition. 2. Reactive oxygen species, particularly superoxide anions, invokes endothelial cell activation through...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706055
更新日期:2005-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Animal models of drug-seeking suggest that exposure to cues associated with self-administered drugs and drug primes might precipitate relapse via activation of central dopaminergic substrates. EXPERIMENTAL APPROACH:The effects of priming injections of dopamine and 5-HT agonists on drug-seeking a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01193.x
更新日期:2011-04-01 00:00:00
abstract::1. Acute moderate hypoxia modifies the catalytic activity and expression of certain isoenzymes of hepatic cytochrome P450 (P450). The aim of this study was to document whether hypoxia affects hepatic P450 directly or through the release of serum mediators. 2. Rabbits were subjected to a FiO(2) of 8% for 48 h, sacrific...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704933
更新日期:2002-11-01 00:00:00
abstract::1. The effects of the two enantiomers, quinidine and quinine, were studied on depolarization- and agonist-induced isometric contractions in rat isolated thoracic aortic rings. 2. Quinidine or quinine (10(-6)M-3 x 10(-4)M) produced a concentration-dependent relaxation of 80 mM KCl-contracted rings, the pD2 values being...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15161.x
更新日期:1996-01-01 00:00:00
abstract::1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11993.x
更新日期:1989-06-01 00:00:00
abstract::1. The action of adrenaline on the K(+) balance of the isolated heart was found to depend on the ionic composition and the temperature of the perfusion fluids used.2. When the perfusion fluid contained 145 mM Na(+), 1.7 mM Ca(++) and 3-9 mM K(+), adrenaline caused the hearts to gain K(+); when the K(+) concentration w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08012.x
更新日期:1969-07-01 00:00:00
abstract::1. In guinea-pig isolated bronchus treated with indomethacin (2.8 microM), electrical field stimulation (EFS; 10 Hz, 0.5 ms, 60-70 V, for 10 s) evoked a tetrodotoxin (3 microM)-sensitive, biphasic contraction comprising a rapid, atropine (1 microM)-sensitive cholinergic response succeeded by a slowly developing, capsa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09081.x
更新日期:1992-04-01 00:00:00
abstract::1. Ginsenosides, the active ingredients extracted from Panax ginseng, have been shown to promote nitric oxide (NO) release in bovine aortic endothelial cells. Since the endothelial cells and the perivascular nerves in penile corpus cavernosum contain NO synthase and an NO-like substance has been shown to be released f...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16313.x
更新日期:1995-05-01 00:00:00
abstract::1. Skins of the lizard Anolis carolinensis darken in vitro in response to melanophore stimulating hormone (MSH), a peptide hormone, as well as to catecholamines. These hormones darken Anolis skins by dispersing the sub-cellular organelle, the melanosome, out into the dendritic processes of the dermal melanophores.2. D...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09565.x
更新日期:1970-05-01 00:00:00
abstract::1. The effects of long-term treatment with trandolapril, an angiotensin I-converting enzyme inhibitor, on exercise capacity of rats with chronic heart failure (CHF) following coronary artery ligation were examined. CHF was developed by 8 weeks after the coronary artery ligation. 2. The running time of rats with CHF in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702471
更新日期:1999-04-01 00:00:00
abstract::Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are canonically activated by oxidized derivatives of cholesterol. Since the mid-90s, numerous groups have identified LXRs as endocrine receptors that are involved in the regulation of various physiological functions. As a result, when their ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15286
更新日期:2020-10-20 00:00:00
abstract::1. The endothelium-dependent relaxants acetylcholine (ACh; 0.03-10 microM) and A23187 (0.03-10 microM), and nitric oxide (NO), applied either as authentic NO (0.01-10 microM) or as the NO donors 3-morpholino-sydnonimine (SIN-1; 0.1-10 microM) and S-nitroso-N-acetylpenicillamine (SNAP; 0.1-10 microM), each evoked conce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701746
更新日期:1998-04-01 00:00:00
abstract::1. Experiments were designed to investigate the effects of the inducible nitric oxide synthase (iNOS) stimulator, lipopolysaccharide (LPS), on noradrenaline (NA) responses and on NOS activity and its expression in intact mesenteric resistance arteries (MRAs) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703552
更新日期:2000-09-01 00:00:00
abstract::1. The purpose of this study was to determine the in vivo inhibitory efficacy of azapropazone on neutrophil migration. The effects of azapropazone given at a dose of 100 mg kg-1 i.v. every 2 h on the neutrophil migration into skin inflammation sites (blister fluid) as well as into an autologous serum (+/- chemoattract...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14686.x
更新日期:1990-02-01 00:00:00
abstract::1. The vasodilator effects of arginine, nitric oxide (NO), acetylcholine (ACh) and sodium nitroprusside (NP) in the noradrenaline-preconstricted ('high tone') perfused rat kidney have been examined. 2. L-Arginine (0.6-23 mumol) caused a biphasic change in renal perfusion pressure. D-Arginine (0.6-23 mumol) was without...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12011.x
更新日期:1989-07-01 00:00:00
abstract::1. The binding of 1,3-[3H]-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), an antagonist radioligand selective for adenosine A1 receptors, was studied in rat duodenum, colon muscularis mucosae and longitudinal muscle, urinary bladder and vasa deferentia. 2. [3H]-DPCPX bound with high affinity to a single site in all memb...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17132.x
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13007
更新日期:2015-03-01 00:00:00
abstract::1. Turning behaviour after unilateral lesions of the nigro-striatal dopamine pathway in rats has been used to compare the actions of cocaine and desipramine on central dopamine-containing neurones.2. Administration of cocaine alone (5-20 mg/kg) resulted in no turning or minimal turning towards the lesioned side; the m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08156.x
更新日期:1973-01-01 00:00:00
abstract::1. Nine non-steroidal anti-inflammatory drugs were tested for antagonism of bradykinin-induced bronchoconstriction in guinea-pig lungs in vivo. Only one, benzydamine, was inactive.2. The descending order of potency of the active anti-inflammatory drugs was meclofenamate = Scha 306>Scha 87/2>indoxole>Mi85>indomethacin>...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb07952.x
更新日期:1968-09-01 00:00:00
abstract::Although cyclosporin (CsA) is considered to be the best immunosuppressive molecule in transplantation, it has been suspected to alter mitochondrial respiration of various tissues. We evaluated the acute effect of CsA and its vehicle on maximal oxidative capacity (V(max)) of cardiac, soleus and gastrocnemius muscles of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704129
更新日期:2001-07-01 00:00:00
abstract::Cyclic adenosine monophosphate (cAMP) is one of the second messengers critically involved in the molecular mechanisms underlying memory formation. In the CNS, the availability of cAMP is tightly controlled by phosphodiesterase 4 (PDE4), a family of enzymes that degrades the cyclic nucleotide to inactive AMP. Among the...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13257
更新日期:2015-10-01 00:00:00
abstract::1. The effects of pregnancy on mesenteric arterial function were examined in constantly perfused (5 ml min-1) mesenteric arterial beds isolated from 21-day pregnant rats. The function of sympathetic and sensory-motor perivascular nerves, endothelium and smooth muscle was examined. The role of nitric oxide and prostagl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15307.x
更新日期:1996-04-01 00:00:00
abstract::1. The effects of some chloride channel antagonists were studied on the calcium-activated chloride current (ICl(Ca)) in smooth muscle cells from the rabbit portal vein with the perforated patch technique. 2. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) and 4,4'-diisothiocyanato-stilbene-2,2'-disu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14891.x
更新日期:1994-04-01 00:00:00
abstract::Rat vas deferens preparations became desensitized to the alpha 1-adrenoceptor antagonist thymoxamine: after 6 h in vitro, the t 1/2 value (time to attain half the occupancy of receptors occupied at equilibrium) of the response to this drug was 1.50 fold greater in control strips (strips exposed to thymoxamine at 6 h) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10113.x
更新日期:1984-09-01 00:00:00
abstract::1 The actions of 4-(2-hydroxy-3-isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new beta-adrenoceptor blocking drug, on the twitch response of the isolated papillary muscle of the rabbit and on dP/dt max and free heart rate of a denervated dog heart preparation, are described.2 ICI 66082 (up to 1 mg/ml) did not...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09644.x
更新日期:1974-06-01 00:00:00
abstract::Excessive death of cardiac myocytes leads to many cardiac diseases, including myocardial infarction, arrhythmia, heart failure and sudden cardiac death. For the last several decades, most work on cell death has focused on apoptosis, which is generally considered as the only form of regulated cell death, whereas necros...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14363
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Leucocyte infiltration is a rate-limiting step in the pathophysiology of acute pancreatitis (AP) although the adhesive mechanisms supporting leucocyte-endothelium interactions in the pancreas remain elusive. The aim of this study was to define the role of lymphocyte function antigen-1 (LFA-1) in ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01225.x
更新日期:2011-05-01 00:00:00