We investigated the effect of a nitric oxide (NO)-releasing derivative of aspirin (NCX-4016) on a mitochondria-dependent model of apoptosis in human umbilical endothelial cells (HUVEC). Exposure of HUVEC to staurosporine caused a progressive fall in mitochondrial membrane potential (DeltaPsi(m)) and apoptosis. Exposure to an NO donor, (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium...

The effect of beta-adrenergic stimulation on cardiac Na(+)/Ca(2+) exchange has been controversial. To clarify the effect, we measured Na(+)/Ca(2+) exchange current (I(NCX)) in voltage-clamped guinea pig, mouse, and rat ventricular cells. When I(NCX) was defined as a 5 mM Ni(2+)-sensitive current in guinea pig ventricular myocytes, 1 microM isoproterenol apparently augmented I(NCX) by approximat...

BACKGROUND NCX-4016 is an acetylsalicylic acid (ASA) derivative containing a nitric oxide-releasing moiety. Compared with ASA, NCX-4016 has a broader spectrum of antithrombotic and antiinflammatory activities. We hypothesized that NCX-4016 might inhibit in vivo lipopolysaccharide (LPS)-induced expression of tissue factor (TF). METHODS AND RESULTS Rats were administered 90 mg/kg NCX-4016 orall...

Enhanced airway contractility following inflammation by cytokines such as tumor necrosis factor alpha (TNFα) or interleukin-13 (IL-13) involves increased intracellular Ca(2+) ([Ca(2+)](i)) levels in airway smooth muscle (ASM). In ASM, plasma membrane Ca(2+) fluxes form a key component of [Ca(2+)](i) regulation. There is now growing evidence that the bidirectional plasma membrane Na(+)/Ca(2+) ex...

We investigated the roles and relationships of plasma membrane Ca(2+)-ATPase (PMCA), sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2, and Na(+)/Ca(2+) exchanger (NCX) in bladder smooth muscle contractility in Pmca-ablated mice: Pmca4-null mutant (Pmca4(-/-)) and heterozygous Pmca1 and homozygous Pmca4 double gene-targeted (Pmca1(+/-)Pmca4(-/-)) mice. Gene manipulation did not alter the amou...

OBJECTIVE Metabolic inhibition causes a decline in mechanical performance and, if prolonged, myocardial contracture and cell death. The decline in mechanical performance is mainly due to altered intracellular calcium handling, which is under control of the Na(+)/Ca(2+)-exchanger (NCX) The driving force of the NCX (ΔG(ncx)) determines the activity of NCX. The aim of this study was to describe th...

q 2q Ž . 2q Objective: The cardiac sarcolemmal Na rCa -exchanger NCX plays an important role in the maintenance of the myocardial Ca homeostasis which is altered in cardiac hypertrophy and failure. The aim of the present study was to investigate whether a-adrenergic stimulation known to induce cardiac hypertrophy might be involved in the regulation of the sarcolemmal NCX. Methods: Adult rat Ž ....

We previously showed that NCX 4040 inhibits in vitro and in vivo tumor growth and induces apoptosis in human colon cancer cell lines. On the basis of these results, NCX 4040 antitumor activity in combination with 5-fluorouracil (5-FU) or oxaliplatin was evaluated in vitro and in vivo in human colon cancer models. The cytotoxicity of different NCX 4040 and 5-FU or oxaliplatin combination schemes...

Increased Na/Ca exchange (NCX) expression may be part of the genetic reprogramming in cardiac remodeling. In this review we address the following questions: (1) Is increased NCX activity a general feature of cardiac remodeling in hypertrophy and heart failure? (2) How does this contribute to the contractile and electrical phenotype of hypertrophy and heart failure? (3) Should be consider NCX a ...

Background—The Na/Ca exchange (NCX) extrudes Ca from cardiac myocytes, but it can also mediate Ca influx, load the sarcoplasmic reticulum with Ca, and trigger Ca release from the sarcoplasmic reticulum. In ischemia/ reperfusion or digitalis toxicity, increased levels of intracellular [Na] ([Na]i) may raise levels of intracellular [Ca ] ([Ca]i) via NCX, leading to cell injury and arrhythmia. Met...