Abstract：
:The objective of this study was to determine the mechanism by which Na(+)/H(+) exchanger (NHE) inhibitors induce vasodilatation. The NHE inhibitors, 5-(N,N-dimethyl)-amiloride (DMA), cariporide, and amiloride, evoked endothelium-dependent relaxation in rat aortas with ED50 values of 16, 89, and 148μM, respectively, and these effects were abolished by treatment with N(G)-nitro-l-arginine methyl ester (L-NAME). The relaxation effects induced by DMA and cariporide were strongly attenuated in aortas of the endothelial NO synthase (eNOS)-deficient mice, as compared to the effects in wild-type mice. The DMA-induced relaxation in rat aorta was attenuated by a calmodulin (CaM) inhibitor, calmidazolium, and a soluble guanylyl cyclase inhibitor, [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, but was not affected by a phosphoinositide 3-kinase inhibitor, wortmannin. Immunoblots for endothelial eNOS on immunoprecipitated CaM complexes showed that DMA enhanced the association of eNOS with CaM in rat aortas. Both DMA and cariporide induced the reduction of intracellular pH (pHi) in bovine aortic endothelial cells (BAECs), which was accompanied by a sustained elevation of cytosolic Ca(2+) ([Ca(2+)]i). This DMA-induced rise of [Ca(2+)]i was not affected by removing external Ca(2+) from the buffer, but was abolished in thapsigargin-pretreated BAECs. These results suggest that lowering of pHi by NHE inhibitors in endothelial cells induces the mobilization of Ca(2+) from the thapsigargin-sensitive stores of endoplasmic reticulum, which in turn stimulates NO production via the CaM-dependent activation of eNOS.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Sasahara T,Yayama K,Matsuzaki T,Tsutsui M,Okamoto Hdoi
10.1016/j.vph.2012.11.004subject
Has Abstractpub_date
2013-04-01 00:00:00pages
319-25issue
4eissn
1537-1891issn
1879-3649pii
S1537-1891(12)00202-9journal_volume
58pub_type
杂志文章abstract：:While brain-derived neurotrophic factor (BDNF) was previously reported to induce relaxation of conduit artery, whether the BDNF/TrkB (tropomyosin-related kinase) pathway is involved in the tone control of resistance arteries is not known. This study investigated TrkB receptors levels/localization and the vasomotor eff...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2018.02.005
更新日期：2018-07-01 00:00:00
abstract：:Cardiac muscle extends into mammalian pulmonary veins for variable distances according to species. This study has addressed the autonomic control of electrically paced cardiac muscle of the pulmonary vein of the rat. Contractile responses of Wistar rat pulmonary veins were investigated under isometric conditions in vi...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2006.09.005
更新日期：2007-03-01 00:00:00
abstract：:Propionyl-l-carnitine (PLC) is a natural short-chain derivative of l-carnitine (LC), a natural amino acid that plays an important role in fatty acid metabolism. Recent studies suggest that PLC has vascular protective effects. Because of the importance of endothelial nitric oxide synthase (eNOS) and its product, antiat...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2013.07.001
更新日期：2013-09-01 00:00:00
abstract：:Recent studies evidence that peroxynitrite is spontaneously formed when nitric oxide (NO) and superoxide coexist and suggest that it is likely to be involved in the destruction of the pancreatic beta cells. We examined whether drugs that inhibit nitric oxide synthase (NOS) or scavenge peroxynitrite could abrogate STZ-...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00212-4
更新日期：2002-03-01 00:00:00
abstract：:Animal studies have identified monocyte chemoattractive protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) as critical mediators of arterial diameter enlargement in response to chronic increases in blood flow (arteriogenesis). Furthermore, cellular studies have shown that the shear stresses resulting from...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2008.11.005
更新日期：2009-03-01 00:00:00
abstract：:tert-Butyl hydroperoxide (t-BOOH), a membrane permeant oxidant, elicits enhanced vasoconstriction of perfused kidney and mesenteric arterial beds isolated from DOCA-salt-induced hypertensive rats. We hypothesize that enhanced vasoconstriction to t-BOOH during DOCA-salt hypertension involves free radical species and de...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00309-9
更新日期：2003-01-01 00:00:00
abstract：:There is evidence that dihydropyridine calcium antagonists (DHP) play a beneficial role during the development of atherosclerosis. Since antioxidative properties of this substance class may be important, we investigated the antioxidative potency of the DHP prototype calcium channel antagonist nifedipine, the long acti...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2004.11.003
更新日期：2005-03-01 00:00:00
abstract：:This study was designed to study the influence of Sacoglottis gabonensis stem bark extract on the metabolic and cytotoxic side effects of 2,4-dinitrophenyl hydrazine (2,4-DNPH) on the brain and blood using male weaving rats as the experimental model. This was after the effect of the bark extract and bergenin, its isol...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(03)00042-9
更新日期：2002-12-01 00:00:00
abstract：:Unresolved endoplasmic reticulum (ER) stress, with the subsequent persistent activation of the unfolded protein response (UPR) is a well-recognized mechanism of endothelial cell apoptosis with a major impact on the integrity of the endothelium during the course of cardiovascular diseases. As in other cell types, Ca(2+...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.07.011
更新日期：2016-01-01 00:00:00
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journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2010.03.002
更新日期：2010-07-01 00:00:00
abstract：:In addition to its role as a vasoconstrictor, angiotensin II also acts as a potent growth factor by activating several tyrosine kinases, including Jak2. Interestingly, Jak2 has been linked to similar cardiovascular pathologies as have been previously linked to the renin-angiotensin system. Identifying the downstream t...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.08.022
更新日期：2005-11-01 00:00:00
abstract：:Prostaglandin E2 (PGE2), a cyclooxygenase metabolite that generally acts as a systemic vasodepressor, has been shown to have vasopressor effects under certain physiologic conditions. Previous studies have demonstrated that PGE2 receptor signaling modulates angiotensin II (Ang II)-induced hypertension, but the interact...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2016.05.015
更新日期：2016-09-01 00:00:00
abstract：:Therapeutic modulation of angiogenesis is believed to be a prospective powerful treatment strategy to modulate the microcirculation and therefore help millions of patients with cardiovascular and cancer diseases. The often-frustrating results from late-stage clinical studies indicate an urgent need for improved assess...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2018.09.003
更新日期：2019-01-01 00:00:00
abstract：:Successful drug delivery to the central nervous system (CNS) is highly dependent on DMPK as well as physicochemical properties and it is therefore important to characterise these properties and take them into account when designing chemical lead series that act at CNS targets. Since the drug discovery/development proc...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/s1537-1891(02)00203-3
更新日期：2002-06-01 00:00:00
abstract：:Cigarette smoking is implicated as a major risk factor in the development of cardiovascular and cerebrovascular diseases. Creatine kinase (CK) and its isoforms (CK-MM, MB, BB) have been advocated as sensitive markers in the assessment of cardiac and cerebral damage. Therefore, in the present study, we report the isoen...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.01.003
更新日期：2005-01-01 00:00:00
abstract：:The endothelium synthesizes and releases nitric oxide (NO) to maintain homeostatic function. Under basal conditions, endothelium-derived NO maintains a nonthrombogenic surface, prohibits leukocyte attachment, and promotes vascular relaxation. In the setting of clinical syndromes associated with the development of athe...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s1537-1891(02)00250-1
更新日期：2002-05-01 00:00:00
abstract：:Stem cells possess the ability of self-renewal and give rise to specific cell types. The differentiation of stem cells involves environmental factors, transduction of extra and intra-cellular signals, regulation of gene expression by transcriptional factors, microRNAs and chromosome structural modifiers. Vascular SMCs...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2012.02.014
更新日期：2012-05-01 00:00:00
abstract：:Thalidomide is an antiangiogenic drug and is clinically useful in a number of cancers. However, the molecular mechanism by which thalidomide exerts its antitumor effects is poorly understood. This study was designed to clarify the relationship between antiangiogenesis and antitumor effects of thalidomide and to explor...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.04.003
更新日期：2005-08-01 00:00:00
abstract：:Elevated plasma levels of factor VII and fibrinogen are risk factors for cardiovascular disease, especially arterial thrombosis. Oral contraceptive use increases factor VII and fibrinogen plasma levels. It has been described that DNA polymorphisms are associated with the plasma levels of hemostatic variables and their...
journal_title：Vascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s1537-1891(02)00300-2
更新日期：2002-08-01 00:00:00
abstract：:MicroRNAs (e.g., miRNAs), endogenously expressed small non-coding RNAs, control gene expression by regulating target messenger RNA at post-transcriptional level. Recent studies have identified a specific role for microRNAs as key regulators of vascular function and dysfunction. The zebrafish (Danio rerio) system is a ...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2011.08.224
更新日期：2011-10-01 00:00:00
abstract：:Small GTPase Rap1 has been extensively studied in vitro and shown to regulate multiple basic cellular processes. Until recently, the best studied aspect of Rap1 function in endothelial cells involved its role in regulation of cell-cell junction formation and remodeling. These in vitro studies have increased understand...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2010.03.003
更新日期：2010-07-01 00:00:00
abstract：:Endothelin (ET-1) is chronically elevated in diabetes. However, role of ET-1 in increased oxidative stress in type 2 diabetes is less clear. This study tested the hypotheses that: 1) oxidative stress markers are increased and total antioxidant capacity is decreased in diabetes, and 2) activation of ET(A) receptors med...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2007.05.006
更新日期：2007-08-01 00:00:00
abstract：:Lactadherin is a small (53-66kDa) multifunctional glycoprotein belonging to the secreted extracellular matrix protein family. It has a multi-domain structure and is involved in many biological and physiological processes, including phagocytosis, angiogenesis, atherosclerosis, tissue remodeling, and haemostasis regulat...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2017.11.006
更新日期：2018-02-01 00:00:00
abstract：:The present study was undertaken to investigate endothelial function and epoxyeicosatrienoic acids (EETs), which is a cytochrome P-450 monooxygenase (CYP) metabolite and one of the candidates as an endothelium-derived hyperpolarizing factor (EDHF) in the renal artery isolated from short-term hypercholesterolemic rabbi...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.03.005
更新日期：2005-06-01 00:00:00
abstract：:Norepinephrine (NE) responses are larger in renal and femoral veins compared to phenylephrine (PE). These differences may be due to the subtypes of adrenoceptor involved in these responses or to the involvement of local modulatory mechanisms. Therefore, the present study investigated in organ bath the adrenoceptor sub...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.06.017
更新日期：2015-09-01 00:00:00
abstract：:We recently demonstrated that lipoic acid suppresses endotoxin-stimulated expression of inducible nitric oxide synthase and nitric oxide production in mouse macrophages. In this study, we tested whether lipoic acid suppresses these inflammatory mediators in the lungs of rats. Rats were assigned to receive either no sp...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.08.005
更新日期：2005-12-01 00:00:00
abstract：:The A3 adenosine receptor (A3AR) is attributed with multiple beneficial actions in ischemic-reperfused myocardium, including modulation of oncotic and apoptotic cell death and enhancement of contractile function. Additionally, the A3AR may attenuate vascular dysfunction and improve long-term outcome from myocardial in...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2005.02.009
更新日期：2005-04-01 00:00:00
abstract：:Activation of ATP-sensitive K+ channels (K ATP) during ischemia leads to arrhythmias and blockade of these channels exert antiarrhythmic action. In this study, we investigated the effects of HMR1098, a sarcolemmal K ATP channel blocker and 5-hydroxydeconoate (5-HD), a mitochondrial K ATP channel blocker on cardiac fun...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2005.11.006
更新日期：2006-04-01 00:00:00
abstract：:Peroxisome proliferator-activated receptors (PPAR)alpha, gamma and beta/delta belong to the nuclear receptor family of ligand-activated transcription factors. PPARs heterodimerize with the retinoid X receptor (RXR) and then act as transcription factors to modulate the function of many target genes. PPARalpha, gamma an...
journal_title：Vascular pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.vph.2005.11.014
更新日期：2006-07-01 00:00:00
abstract：:Cardiovascular diseases are the major challenge to modern medicine. Intervention to cardiovascular cells is crucial for treatment of the diseases. Here we report a novel intervention to vascular smooth muscle (VSM) cells by optogenetics. Channelrhodopsin in a tandem with YFP was selectively expressed in smooth muscle ...
journal_title：Vascular pharmacology
pub_type： 杂志文章
doi：10.1016/j.vph.2015.03.006
更新日期：2015-08-01 00:00:00
