Abstract:
PURPOSE OF THE RESEARCH:Overexpression of the human dimethylarginine dimethylaminohydrolase type 1 (hDDAH1) gene was reported to have beneficial cardiovascular effects in mice. To date, it is unclear whether these effects are related to enhanced metabolic clearance of asymmetric dimethylarginine (ADMA) and l-N(G)-mono-methyl-l-arginine (l-NMMA) or increased DDAH1 expression and activity in cardiovascular tissues of hDDAH1 transgenic mice. PRINCIPAL RESULTS:DDAH activity (DDAH1+DDAH2) was found to be markedly increased in aortic and heart tissues but unaltered in liver and kidney tissues of hDDAH1 transgenic as compared to wild-type (WT) mice. In WT mice, DDAH activity was more abundant in liver and kidney as compared to aorta and heart, suggesting a possible ceiling effect of activity which was unsurpassed by hDDAH1 overexpression. MAJOR CONCLUSIONS:Overexpression of hDDAH1 in healthy mice does not result in an improved DDAH-metabolic capacity of kidney and liver under normal, i.e. unchallenged conditions. The most likely explanation for low ADMA and l-NMMA concentrations in hDDAH1 transgenic mice is a decreased release of ADMA from aorta, heart, and possibly other organs. The protective cardiovascular effects seen in these animals may therefore be related to an improved activity of the DDAH enzyme in the cardiovascular system and not be related to improved renal and hepatic clearance of ADMA and l-NMMA.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Schwedhelm E,von Leitner EC,Atzler D,Schmitz C,Jacobi J,Meinertz T,Münzel T,Baldus S,Cooke JP,Böger RH,Maas R,Sydow Kdoi
10.1016/j.phrs.2009.08.001subject
Has Abstractpub_date
2009-12-01 00:00:00pages
494-502issue
6eissn
1043-6618issn
1096-1186pii
S1043-6618(09)00196-0journal_volume
60pub_type
杂志文章abstract::One of the most serious side effects of the immunosuppressive agent, cyclosporin A (CsA), is drug-related hypertension. As it is generally accepted, the sympathetic nervous system may play an important role in the development or maintenance of this abnormal pathophysiological situation. This study is aimed at assessin...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0572
更新日期:2000-02-01 00:00:00
abstract::Segetoside I is a plant-derived bisdesmosidic saponin from Vaccaria segetalis (Neck) with reported anticancer activities. This development has raised an interest in the therapeutic potential of segetoside I. Here, we report the in vitro and in vivo antitumor activities of segetoside I against some selected cancer cell...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.04.032
更新日期:2016-08-01 00:00:00
abstract::Heparin-binding protein (HBP; CAP37/azurocidin) is secreted from neutrophil leukocytes early during inflammation and plays a central role in early capillary leakage and extravasation of neutrophils. Furthermore, HBP is chemotactic towards monocytes and lymphocytes and protects against stress-induced apoptosis, e.g. in...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.01.004
更新日期:2005-06-01 00:00:00
abstract::Tumor metastasis is a key cause of cancer mortality, and inhibiting migration of cancer cells is one of the major directions of anti-metastatic drug development. Calumenin and fibulin-1 are two extracellular proteins that synergistically inhibit cell migration and tumor metastasis, and could potentially be served as t...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2015.05.001
更新日期:2015-09-01 00:00:00
abstract::The smoothened (SMO) receptor, an essential signal transducer in the Hedgehog pathway, was targeted with antagonists to suppress the tumor. It is interesting that SMO D473H mutation confers resistance on inhibitor LDE-225 rather than LEQ-506. In this paper, the binding modes of them against the wild type and mutant SM...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2017.11.025
更新日期:2018-03-01 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::The aim of this review is to underline the redundancy of down-regulation pathways for p53, at the light of the two more important degradative systems: calpains and ubiquitin-dependent pathways. The MDM2 feed-back loop is also illustrated, as well as the phosphorylative/dephosphorylative regulation of the latent and ac...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1006/phrs.1997.0269
更新日期:1998-02-01 00:00:00
abstract::Growth differentiation factor 11 (GDF11) is a novel factor with controversial effects on cardiac hypertrophy both in vivo and in vitro. Although recent evidence has corroborated that GDF11 prevents the development of cardiac hypertrophy, its molecular mechanism remains unclear. In our previous work, we showed that nor...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104273
更新日期:2019-08-01 00:00:00
abstract::Steroids (aldosterone and testosterone) and peptides of cerebral origin (angiotensin II and the tachykinins) control the salt intake of the rat. They arouse or suppress the behaviour and produce life-long enhancements of NaCl intake. Need-induced salt intake (salt appetite or salt hunger), which is the consequence of ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/1043-6618(92)91380-y
更新日期:1992-02-01 00:00:00
abstract::The altered vascular responses to various vasopressors and relaxants have been well reported in various animal models of hypertension, insulin resistance and diabetes. Though the role of oxidative stress (increased superoxide levels) associated with these altered vascular responses in hyperglycemic/diabetic state is w...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.11.002
更新日期:2006-03-01 00:00:00
abstract::Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. Although the results of clinical studies indicate considerable disparity in the analgesic efficacy of NSAIDs, the pre-clinical models generally used for the study of nociception do not allow a clear distinction to be made between the ana...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2001.0921
更新日期:2002-02-01 00:00:00
abstract::Etifoxine (EFX) is a non-benzodiazepine psychoactive drug which exhibits anxiolytic effects through a dual mechanism, by directly binding to GABAA receptors (GABAARs) and to the mitochondrial 18-kDa translocator protein, resulting in the potentiation of the GABAergic function. The β subunit subtype plays a key role in...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.04.034
更新日期:2019-07-01 00:00:00
abstract::The present study was undertaken to characterize the interactions between nonsteroidal anti-inflammatory drugs and the alpha(2)-adrenoceptor agonist clonidine in an acute nociceptive test. The writhing test was selected as a model of acute visceral pain. Isobolograms were constructed to assess the interactions of clon...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2004.02.008
更新日期:2004-09-01 00:00:00
abstract::Previous studies have suggested additional beneficial effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors including the lipid-lowering effect; however, results on lipid profile are controversial. Thus, this meta-analysis aimed to determine the effect of SGLT2 inhibitors treatment on lipid levels in patients ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.105068
更新日期:2020-10-01 00:00:00
abstract::A decrease in constitutive nitric oxide synthase (cNOS) activity occurred with decreases in hexosamine (an index of mucus synthesis) and adherent mucus (an index of mucus secretion) concentrations in the gastric mucosa of rats with water immersion restraint (WIR) stress. The decreases in gastric mucosal hexosamine and...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1998.0379
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Chronic obstructive pulmonary disease (COPD) is characterized by progressive alveolar damage and generally irreversible airflow limitation. Nuclear factor-κB (NF-κB) plays a critical role in COPD pathogenesis. Receptor-interacting protein 2 (Rip2), a 60 kDa adaptor protein, is a positive regulato...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.10.016
更新日期:2019-01-01 00:00:00
abstract:OBJECTIVE:Nuclear factor (NF)-kappaB is a ubiquitous transcription factor that can be activated by multiple signals. To elucidate the role of NF-KB and the effects of NF-kappaB inhibitor on ureteric damages in obstructive uropathy, we conducted this study. METHODS:The expressions of NF-kappaBp50, NF-kappaBp65, interle...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2009.05.004
更新日期:2009-10-01 00:00:00
abstract::The aim of this study was to verify the role of Vitamins C and E on the cognitive function of young and aged mice. First and second groups of young animals (aged 3 months) received either Vitamin E (250mg/kg per day) or Vitamin C (300mg/kg per day) for 60 days. Third group was treated with the combination of Vitamin E...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2003.10.004
更新日期:2004-03-01 00:00:00
abstract::In this study, we evaluated anti-hyperglycemic effect and body weight reduction activity of Gymnema yunnanense extract in obese ob/ob and diabetic db/db mice. Animals received daily intraperitoneal injections of the extract 100 mg/kg for 12 days. On Day 5, the extract-treated ob/ob mice had significantly lower fasting...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(02)00322-5
更新日期:2003-04-01 00:00:00
abstract::Diabetes mellitus is an important risk factor for the development of cardiovascular disease. The impact of diabetes on the heart in part resides in the changes in metabolic fuel availability evoked by lack of insulin or resistance to its action. This review addresses how the metabolic abnormalities associated with poo...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2009.04.006
更新日期:2009-09-01 00:00:00
abstract::We investigated the anti-platelet effect of a newly synthesized guanidine derivative KR-32560, a sodium/hydrogen exchanger-1 (NHE-1) inhibitor, together with the elucidation of the possible mode of action. KR-32560 concentration dependently inhibited the aggregation of washed rabbit platelets induced by collagen (10 m...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.12.003
更新日期:2006-03-01 00:00:00
abstract::Myocardial infarction (MI) is a major cause of morbidity and mortality in western countries and the formation of intracoronary thrombi is recognized as a critical determinant of this ischaemic event. Since streptokinase and urokinase cause in vitro lysis of clots, it was though that these drugs were also effective in ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/1043-6618(89)90233-8
更新日期:1989-03-01 00:00:00
abstract::The insulinotropic action of several new esters of succinic acid was assessed in isolated rat islets incubated in the presence of 7 mM D-glucose. An efficient secretory response was observed with the monobenzyl, monoisopropyl, monoallyl, monopropyl, monoethyl, monobutyl, dibutyl, dipropyl and diallyl esters of succini...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1996.0038
更新日期:1996-04-01 00:00:00
abstract::The concept of compartment evolved in the contexts of radioactivity, physiology, pharmacology and tracer kinetics. Recently compartmental models have been compared with 'physiological models', even though in most cases the same, or stricter hypotheses, are necessary for the validity of these latter models. This paper ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2001.0873
更新日期:2001-10-01 00:00:00
abstract::A global transcriptional regulator, MgrA, was previously identified as a key determinant of virulence in Staphylococcus aureus. An 80% EtOH extract of Uncaria gambier was found to attenuate the virulence of S. aureus via its effects on MgrA. Using bioassay-guided fractionation, a polyphenolic polymer, uncariitannin, w...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104328
更新日期:2019-09-01 00:00:00
abstract::A new class of methylfuroxans and methylfurazans arylthio, arylsulphinyl and arylsulphonyl substituted, characterized by vasodilating and antiaggregatory properties, is described. Vasodilating activity, tested on rabbit aortic rings percontracted with 1 microM noradrenaline, is enhanced by N-oxidation of the furazan r...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1993.1123
更新日期:1993-10-01 00:00:00
abstract::In the present study the effect of ketamine, a dissociative anaesthetic, on the GABA- and on the specific GABAA-agonist muscimol-induced responses of the isolated guinea pig ileum was investigated. GABA as well as muscimol produce a concentration-dependent contractile effect on the duodenum, jejunum and ileum. The sen...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(95)80086-7
更新日期:1995-06-01 00:00:00
abstract::N-acetyl penicillamine (NAP), a derivative of penicillamine and copper chelator has been employed as a potential protector of host stress organ injury during Plasmodium berghei infection in mice. Intramuscular injection of NAP (60 mg kg-1 body wt for 10 days) to P. berghei mice was able to restrict the hepato- and spl...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1997.0233
更新日期:1997-10-01 00:00:00
abstract::The principle of mechanopharmacology of airway smooth muscle (ASM) is based on the premise that physical agitation, such as pressure oscillation applied to an airway, is able to induce bronchodilation by reducing contractility and softening the cytoskeleton of ASM. Although the underlying mechanism is not entirely cle...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.104995
更新日期:2020-09-01 00:00:00
abstract::Mild cognitive impairment (MCI), regarded as the prodromal stage before the clinical phase of Alzheimer's disease (AD), has been considered for early intervention. Unfortunately, many trials in this stage with drugs with single-target turned out to be little or no effect. Multi-targeting in nature based on the theory ...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章
doi:10.1016/j.phrs.2019.104319
更新日期:2019-08-01 00:00:00