Aldosterone abrogates nuclear factor kappaB-mediated tumor necrosis factor alpha production in human neutrophils via the mineralocorticoid receptor.

Mineralocorticoid receptor (MR) activation by aldosterone controls salt homeostasis and inflammation in several tissues and cell types. Whether or not a functional MR exists in polymorphonuclear neutrophils is unknown. We investigated the hypothesis that aldosterone modulates inflammatory neutrophil responses via the MR.

Regulatory T cells ameliorate angiotensin II-induced cardiac damage.

Background: Hypertensive target organ damage, especially cardiac hypertrophy with heart failure and arrhythmia, is a major source of morbidity and mortality. Angiotensin II, a major mediator of hypertension and cardiac damage, has proinflammatory properties. Inflammation and activation of the immune system play a pivotal role in pathogenesis of hypertensive target organ damage.

Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia.

To clarify the role of Angiotensin II (Ang II) in the sensory system and especially in the trigeminal ganglia, we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of Ang II and substance P in the rat and human trigeminal ganglia. The rat trigeminal ganglia expressed substantial amounts of Ang-N- and ACE mRNA as determined by quantitative real time PCR. Renin mRNA was untraceable in rat samples.

Role of the multidomain protein spinophilin in blood pressure and cardiac function regulation.

Spinophilin controls intensity/duration of G protein-coupled receptor signaling and thereby influences synaptic activity. We hypothesize that spinophilin affects blood pressure through central mechanisms. We measured blood pressure and heart rate in SPL-deficient (SPL(-/-)), heterozygous SPL-deficient (SPL(+/-)), and wild-type (SPL(+/+)) mice by telemetry combined with fast Fourier transformation.

Novel role for inhibitor of differentiation 2 in the genesis of angiotensin II-induced hypertension.

Background: Angiotensin (Ang) II-induced target-organ damage involves innate and acquired immunity. Mice deficient for the helix-loop-helix transcription factor inhibitor of differentiation (Id2(-/-)) lack Langerhans and splenic CD8a+ dendritic cells, have reduced natural killer cells, and have altered CD8 T-cell memory. We tested the hypothesis that an alteration in the number and quality of circulating blood cells caused by Id2 deletion would ameliorate Ang II-induced target-organ damage.

Trophoblasts reduce the vascular smooth muscle cell proatherogenic response.

Maternal spiral artery remodeling is the consequence of controlled trophoblast invasive interaction with the maternal cellular environment and is fundamentally important for successful placentation. In preeclampsia, trophoblast invasion is shallow, remodeling is incomplete, and vessels develop an inflammatory appearance, termed "acute atherosis." We noted that, in our preeclampsia, human renin-human angiotensinogen transgenic rat model, complement component 3 (C3), and tumor necrosis factor-alpha were upregulated and heavily expressed in atherotic uteroplacental vessels.

Short-term heat exposure inhibits inflammation by abrogating recruitment of and nuclear factor-{kappa}B activation in neutrophils exposed to chemotactic cytokines.

Cytokines, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-8 attract neutrophils into inflammatory sites. During emigration from the blood neutrophils interact with extracellular matrix proteins such as fibronectin. Fibronectin provides beta2-integrin co-stimulation, allowing GM-CSF and IL-8 to activate nuclear factor (NF)-kappaB, an effect that does not occur in suspension.

Regulator of G protein signalling 2 ameliorates angiotensin II-induced hypertension in mice.

Angiotensin II (Ang II) activates signalling pathways predominantly through the G-protein-coupled Ang II type 1 receptor (AT(1)R). The regulator of G protein signalling 2 (RGS2) is a negative G protein regulator. We hypothesized that RGS2 deletion changes blood pressure regulation by increasing the response to Ang II.

Beta2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-kappaB activation of human neutrophils.

Microparticles from various cells are generated during inflammation. Platelet-derived microparticles (PMPs) harbor receptors that are not genuinely expressed by neutrophils. We tested whether or not functional glycoprotein IIb/IIIa (GPIIb/IIIa) receptors can be acquired by neutrophils via PMPs and whether these receptors participate in pro-inflammatory signaling.

Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage.

Nuclear factor kappa B (NF-kappaB) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell-specific NF-kappaB suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell-restricted NF-kappaB super-repressor IkappaBalphaDeltaN (Tie-1-DeltaN mice) overexpression.

Angiotensin II-induced sudden arrhythmic death and electrical remodeling.

Rats harboring the human renin and angiotensinogen genes (dTGR) feature angiotensin (ANG) II/hypertension-induced cardiac damage and die suddenly between wk 7 and 8. We observed by electrocardiogram (ECG) telemetry that ventricular tachycardia (VT) is a common terminal event in these animals. Our aim was to investigate electrical remodeling.

NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils.

Antineutrophil cytoplasmic antibodies (ANCAs) with specificity for proteinase 3 (PR3) are central to a form of ANCA-associated vasculitis. Membrane PR3 (mPR3) is expressed only on a subset of neutrophils. The aim of this study was to determine the mechanism of PR3 surface expression on human neutrophils.

p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage.

We investigated whether or not p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage. We used double transgenic rats harboring both human renin and angiotensinogen genes (dTGRs). dTGR, with or without p38 inhibitor (BIRB796; 30 mg/kg per day in the diet), and nontransgenic Sprague-Dawley rats were studied in 2 protocols.

Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific expression, and role in renal 20-hydroxyeicosatetraenoic acid formation.

AA (arachidonic acid) hydroxylation to 20-HETE (20-hydroxyeicosatetraenoic acid) influences renal vascular and tubular function. To identify the CYP (cytochrome P450) isoforms catalysing this reaction in the mouse kidney, we analysed the substrate specificity of Cyp4a10, 4a12a, 4a12b and 4a14 and determined sex- and strain-specific expressions. All recombinant enzymes showed high lauric acid hydroxylase activities.

Fever-like temperatures affect neutrophil NF-kappaB signaling, apoptosis, and ANCA-antigen expression.

The neutrophil is pivotal to ANCA vasculitis pathogenesis. Fever frequently complicates ANCA diseases. This study investigated the effects of short-term heat exposure on apoptosis in neutrophils that were treated with LPS, GM-CSF, IL-8, and dexamethasone.

L-Arginine-NO-cGMP signaling following acute liver injury in the rat.

The incidence of liver diseases has increased over the past few years. For this reason, the consequences of induced nitric oxide (NO) synthesis in liver damages warrant further studies. To address this issue, we investigated the expression of key enzymes engaged in the control of NO signaling in the rat liver after carbon tetrachloride (CCl4) intoxication and subsequent regeneration.

Nitric oxide synthase in human skeletal muscles related to defined fibre types.

Skeletal muscle functions regulated by NO are now firmly established. However, the knowledge about the NO synthase (NOS) expression related to a defined fibre type in human skeletal muscles necessitates further clarification. To address this issue, we examined localization of NOS isoforms I, II and III, in human skeletal muscles employing immunocytochemical labeling with tyramide signal amplification complemented with enzyme histochemistry and Western blotting.

Complement activation in angiotensin II-induced organ damage.

We tested whether or not complement activation participates in angiotensin (Ang) II-induced vasculopathy. We used double transgenic rats harboring human renin and angiotensinogen genes (dTGR) with or without losartan or the human renin inhibitor aliskiren. Sprague-Dawley (SD) rats were controls.

Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in double-transgenic rats.

We tested the hypothesis that the renin inhibitor aliskiren ameliorates organ damage in rats transgenic for human renin and angiotensinogen genes (double transgenic rat [dTGR]). Six-week-old dTGR were matched by albuminuria (2 mg per day) and divided into 5 groups. Untreated dTGR were compared with aliskiren (3 and 0.

Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage.

Background: Aldosterone and angiotensin (Ang) II both may cause organ damage. Circulating aldosterone is produced in the adrenals; however, local cardiac synthesis has been reported. Aldosterone concentrations depend on the activity of aldosterone synthase (CYP11B2).

Compartmentalization of NO signaling cascade in skeletal muscles.

Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle.

The effect of fever-like temperatures on neutrophil signaling.

The effect of fever on neutrophils has not been explored. We tested the hypothesis that fever-like temperature spikes affect neutrophil signaling and function. Prior 60 min, 42 degrees C heat exposure inhibited p38 MAPK, ERK, PI3-Kinase/Akt, and NF-kappaB activation in TNF-alpha-challenged suspended neutrophils.

Cardiac gene expression profile in rats with terminal heart failure and cachexia.

About one-half of double transgenic rats (dTGR) overexpressing the human renin and angiotensinogen genes die by age 7 wk of terminal heart failure (THF); the other (preterminal) one-half develop cardiac damage but survive. Our study's aim was to elucidate cardiac gene expression differences in dTGR-THF compared with dTGR showing compensated cardiac hypertrophy but not yet THF. dTGR treated with losartan (LOS) and nontransgenic rats (SD) served as controls.