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.

Lipid mobilization with physiological atrial natriuretic peptide concentrations in humans.

Context: Atrial natriuretic peptide (ANP) in pharmacological concentrations stimulates lipid mobilization in humans.

Objective: The objective was to determine the hemodynamic and metabolic response to physiologically relevant ANP concentrations.

Design: The design was a human physiological study, conducted in 2004.

The impact of anaemia and kidney function in congestive heart failure and preserved systolic function.

Background: The importance of anaemia in chronic heart failure was highlighted recently by different cohort studies. The aim of this study was to assess the prevalence of anaemia and its relationship to renal function, left ventricular function and symptoms of heart failure.

Methods: We surveyed cases of patients admitted to the Department of Cardiology during 22 consecutive months.

Identification of hypertension-related genes through an integrated genomic-transcriptomic approach.

In search for the genetic basis of hypertension, we applied an integrated genomic-transcriptomic approach to identify genes involved in the pathogenesis of hypertension in the Sabra rat model of salt-susceptibility. In the genomic arm of the project, we previously detected in male rats two salt-susceptibility QTLs on chromosome 1, SS1a (D1Mgh2-D1Mit11; span 43.1 cM) and SS1b (D1Mit11-D1Mit4; span 18 cM).

Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection.

Background: Antibodies against HLA antigens cause refractory allograft rejection with vasculopathy in some, but not all, patients.

Methods: We studied 33 kidney-transplant recipients who had refractory vascular rejection. Thirteen had donor-specific anti-HLA antibodies, whereas 20 did not.

Agonistic autoantibodies to the AT1 receptor in a transgenic rat model of preeclampsia.

We used rats transgenic for the human angiotensinogen (hAogen) gene and the human renin (hRen) gene and crossed the strains to produce a model of preeclampsia in the dams. The female (n=9) hAogen x male hRen cross had severe (telemetry-measured) hypertension and albuminuria, which developed during the last trimester of pregnancy and subsided after delivery. The converse cross (n=9) and control (n=9) SD rats did not.

Magnesium supplementation prevents angiotensin II-induced myocardial damage and CTGF overexpression.

Objectives And Design: Magnesium deficiency promotes vasoconstriction and myocardial damage. Recent studies provide evidence that Ang II mobilizes intracellular Mg through AT1 receptor-mediated pathways. We tested the hypothesis of whether magnesium supplementation prevents Ang II-induced myocardial damage and induction of the profibrotic connective tissue growth factor (CTGF).

Autonomic nervous system and blood pressure regulation in RGS2-deficient mice.

Regulator of G protein signaling (RGS2) deletion in mice prolongs signaling by G protein-coupled vasoconstrictor receptors and increases blood pressure. However, the exact mechanism of the increase in blood pressure is unknown. To address this question we tested autonomic nervous system function and blood pressure regulation in RGS2-deficient mice (RGS2-/-).

Activating auto-antibodies against the AT1 receptor in preeclampsia.

Immune mechanisms have been shown to be important in the pathogenesis of preeclampsia. Here, we review our studies of agonistic antibodies against the AT1 receptor in the pathogenesis as well as a pathologic phenotype of this disorder, focusing on observations in our laboratory. We have demonstrated their specificity of the binding by Western blotting, co-localization, and co-immunoprecipitation experiments.

Weight loss and the renin-angiotensin-aldosterone system.

The renin-angiotensin-aldosterone system has been causally implicated in obesity-associated hypertension. We studied the influence of obesity and weight reduction on the circulating and adipose tissue renin-angiotensin-aldosterone system in menopausal women. Blood samples were analyzed for angiotensinogen, renin, aldosterone, angiotensin-converting enzyme activity, and angiotensin II.

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.

Inducible NOS inhibition, eicosapentaenoic acid supplementation, and angiotensin II-induced renal damage.

Background: Cytochrome P450(CYP)-dependent hydroxylation and epoxygenation metabolites of arachidonic acid (AA) influence renal vascular tone, salt excretion, and inflammation. Transgenic rats over expressing both human renin and angiotensinogen genes (dTGR) feature angiotensin II (Ang II)-induced organ damage, increased expression of inducible nitric oxide synthase (iNOS), decreased AA hydroxylation, and epoxygenation. As nitric oxide production via iNOS can inhibit CYP AA metabolism, we tested the hypothesis that by blocking iNOS or by supplementing eicosapentanoic acid (EPA), which can serve as an alternative CYP substrate, Ang II-induced vasculopathy could be ameliorated.

Heritability of free and receptor-bound leptin in normal twins.

Free and receptor-bound leptin may be regulated by different mechanisms. Genes that influence the concentration of these fractions may have an important functional bearing. We determined circulating leptin receptor concentrations, bound as well as free leptin concentrations, and body composition in 24 monozygotic (MZ) and in 22 dizygotic (DZ) twin pairs.

Single nucleotide polymorphism map of five long-QT genes.

We screened a white population for single nucleotide polymorphisms (SNPs) in five long QT syndrome genes, namely, KCNQ1 (LQT1), HERG (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6). We found 35 SNPs, 10 of which have not been previously described. Ten SNPs were in KCNE1, six in HERG, eight in KCNQ1, four in KCNE2, and seven in SCN5A.

Functional consequences of a novel uromodulin mutation in a family with familial juvenile hyperuricaemic nephropathy.

Background: Familial juvenile hyperuricaemic nephropathy (FJHN) is an autosomal-dominant disorder featuring hyperuricaemia, low fractional urate excretion, interstitial nephritis and chronic renal failure. The responsible gene UMOD was recently identified. UMOD encodes for uromodulin or Tamm-Horsfall glycoprotein, the most abundant protein in normal urine.

Influence of St John's wort on catecholamine turnover and cardiovascular regulation in humans.

Background: St John's wort (Hypericum perforatum) is a popular over-the-counter antidepressant. Its antidepressive effect has been attributed in part to inhibition of monoamine transporters and monoamine oxidase, on the basis of in vitro studies.

Methods: In a double-blind, randomized, placebo-controlled, crossover study, 16 healthy subjects (11 men and 5 women; mean age, 31 +/- 5 years) ingested either St John's wort (300 mg three times daily) or placebo for 7 days.

AT1 receptor agonistic antibodies, hypertension, and preeclampsia.

Immunologic mechanisms and putatively circulating mediators of preeclampsia are not a new idea, but are nevertheless compelling. Here we review studies relating to the role of agonistic antibodies that bind the second extracellular loop of the angiotensin II (AII) AT1 receptor in the pathogenesis as well as a pathologic phenotype of this disorder, focusing on observations in our laboratory. These agonistic autoantibodies (AT1-AA) appear with the development of preeclampsia and mostly are gone by 6 weeks after delivery.

Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice.

The Tamm-Horsfall protein (THP; uromodulin), the dominant protein in normal urine, is produced exclusively in the thick ascending limb of Henle's loop. THP mutations are associated with disease; however, the physiological role of THP remains obscure. We generated THP gene-deficient mice (THP -/-) and compared them with wild-type (WT) mice.