Angiotensin-(1-7) upregulates central nitric oxide synthase in spontaneously hypertensive rats.

Increased blood pressure in hypertension is hypothesized to be caused by high sympathetic nervous system (SNS) activity. Since Ang (1-7) exerts an inhibitory neuromodulatory effect on the SNS through a NO-mediated mechanism, we tested the hypothesis that Ang (1-7) alters centrally nitric oxide synthase (NOS) activity and expression in spontaneously hypertensive rats (SHR). Since NOS activity is altered in relation to the development of hypertension in rats, we evaluated the effect of Ang-(1-7) on hypothalamic NOS activity in two different ages in SHR, corresponding to a prehypertensive phase (3-4 weeks) and a established hypertension (13-14 weeks) and compared with age-matched Wistar-Kyoto (WKY) rats.

Properties of antibodies to a synthetic peptide representing an epitope shared by receptors of the type I cytokine family.

Previous works from our laboratory demonstrated that the monoclonal antibody (MAb) called R7B4 is directed to an epitope shared by various receptors corresponding to the type I cytokine receptor family, containing the common motif WSXWS or the homologous F(Y)GEFS. Later a consensus peptide significantly recognized by the MAb was identified and synthesized (sequence HGYWSEWSPE). In the present work, an homologous of the consensus sequence (HHGYWSEWSPE) was conjugated to PADRE adjuvant to produce Ab that could simulate theMAb activity, that is, acting as hormone and/or cytokine antagonists.

Autoimmune hepatitis-like disease in C57BL/6 mice infected with mouse hepatitis virus A59.

Mouse hepatitis virus A59 (MHV A59) induces autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), a soluble cytosolic enzyme present in the liver and kidneys, in various mouse strains. The aim of this work was to amplify and diversify the autoimmune response restricted to FAH through the use of the exogenous adjuvant called PADRE. Accordingly, C57BL/6 mice were chosen, because these animals respond to PADRE better than other mouse strains.

Changes in Na+, K+-ATPase activity and alpha 3 subunit expression in CNS after administration of Na+, K+-ATPase inhibitors.

The expression of Na(+), K(+)-ATPase α3 subunit and synaptosomal membrane Na(+), K(+)-ATPase activity were analyzed after administration of ouabain and endobain E, respectively commercial and endogenous Na(+), K(+)-ATPase inhibitors. Wistar rats received intracerebroventricularly ouabain or endobain E dissolved in saline solution or Tris-HCl, respectively or the vehicles (controls). Two days later, animals were decapitated, cerebral cortex and hippocampus removed and crude and synaptosomal membrane fractions were isolated.

Angiotensin-(1-7) upregulates cardiac nitric oxide synthase in spontaneously hypertensive rats.

It has been shown that angiotensin (ANG)-(1-7) activates nitric oxide synthase (NOS) in isolated ventricular myocytes from normotensive rats. Since many ANG-(1-7) actions are enhanced in situations of increased ANG II activity, as in hypertension, in this study we investigated the in vivo effect of ANG-(1-7) on NOS activity and expression of endothelial (eNOS), neuronal (nNOS), and inducible NOS (iNOS) in ventricles from spontaneously hypertensive rats (SHR). Rats were subjected to a 60-min ANG-(1-7) infusion (0.

STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-alpha2b peptide.

In the search of mimetic peptides of the interferon-alpha2b molecule (IFN-alpha2b), we have previously designed and synthesized a chimeric cyclic peptide of the IFN-alpha2b that inhibits WISH cell proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-alpha2b stimulus.

Losartan exerts renoprotection through NAD(P)H oxidase downregulation in a renovascular model of hypertension.

This study was performed to provide insight into the regulatory role of angiotensin II and arterial pressure on the activity of antioxidant enzymes and oxidative stress generation in the hypertensive kidney from an experimental animal model of renovascular hypertension. Aortic coarcted and sham-operated rats received vehicle, losartan or minoxidil in their drinking water. After 7 d of treatment rats were sacrificed; hypertensive kidneys were excised, and the NAD(P)H oxidase subunits expression, TBARS production, glutathione level and the activity of heme oxygenase-1 and classical antioxidant enzymes, were evaluated.

High-affinity neurotensin receptor is involved in phosphoinositide turnover increase by inhibition of sodium pump in neonatal rat brain.

Phosphoinositide (PI) metabolism is enhanced in neonatal brain by activation of neurotransmitter receptors and by inhibition of the sodium pump with ouabain or endogenous inhibitor termed endobain E. Peptide neurotensin inhibits synaptosomal membrane Na(+), K(+)-ATPase activity, an effect blocked by SR 48692, a selective antagonist for high-affinity neurotensin receptor (NTS1). The purpose of this study was to evaluate potential participation of NTS1 receptor on PI hydrolysis enhancement by sodium pump inhibition.

A cyclic chimeric interferon-alpha2b peptide induces apoptosis in tumor cells.

Interferons alpha (IFNsalpha) are a family of related proteins exhibiting antiviral, antiproliferative and immunoregulatory activities. Although IFNsalpha have been widely employed for the pharmacological treatment of different types of cancer, the therapeutic efficacy occasionally can be diminished by the appearance of side effects, neutralizing antibodies or tumor resistance. In the search of mimetic peptides of the IFN-alpha2b molecule, we have recently synthesized a chimeric cyclic peptide that inhibits IFN-alpha2b binding to its receptor and exerts an IFN-like antiproliferative activity.

The expression of NMDA receptor subunits in cerebral cortex and hippocampus is differentially increased by administration of endobain E, a Na+, K+-ATPase inhibitor.

Previous studies showed that endobain E, an endogenous Na+, K+-ATPase inhibitor, decreases dizocilpine binding to NMDA receptor in isolated membranes. The effect of endobain E on expression of NMDA receptor subunits in membranes of rat cerebral cortex and hippocampus was analyzed by Western blot. Two days after administration of 10 mul endobain E (1 microl = 29 mg fresh tissue) NR1 subunit expression enhanced 5-fold and 2.

Identification, synthesis and properties of a consensus peptide recognized by a monoclonal antibody directed to various type I cytokine receptors.

Previous works demonstrated that the monoclonal antibody (MAb) called R7B4 is directed to an epitope shared by receptors for lactogenic and somatogenic hormones as well as interleukins 2 and 6 (IL-2 and IL-6). The MAb inhibited the biological effects of those hormones and cytokines by impairing their binding to receptors. It is known that the receptors for growth hormones (GH), prolactins (PRL), IL-2, and IL-6 pertain to the type I cytokine receptor family, sharing the common motif WSXWS or the homologous F(Y)GEFS.

Increased hypothalamic angiotensin-(1-7) levels in rats with aortic coarctation-induced hypertension.

Since angiotensin (Ang) (1-7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1-7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1-7) compared with the normotensive group, with Ang II being the predominant peptide in heart and kidney. In the hypothalamus, equimolar amounts of Ang II and Ang-(1-7) were found in the sham group, whereas only Ang-(1-7) levels increased in CH rats.

Angiotensin-(1-7) blocks the angiotensin II-stimulated superoxide production.

Angiotensin (Ang)-(1-7), a bioactive compound of the renin-angiotensin system, exerts effects leading to blood pressure reduction which counterbalance Ang II pressor actions. The present study was conducted to examine Ang-(1-7) and Ang II effects on superoxide anion production in rat aorta using the lucigenin chemiluminescence method. Ang II dose-dependently increased superoxide anion formation when compared to control levels; a maximal increase (2.

Angiotensin-(1 7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: role of the AT1 and Mas receptors.

Angiotensin (ANG) II exerts a negative modulation on insulin signal transduction that might be involved in the pathogenesis of hypertension and insulin resistance. ANG-(1-7), an endogenous heptapeptide hormone formed by cleavage of ANG I and ANG II, counteracts many actions of ANG II. In the current study, we have explored the role of ANG-(1-7) in the signaling crosstalk that exists between ANG II and insulin.

Phosphoinositide hydrolysis increase by angiotensin-(1--7) in neonatal rat brain.

Angiotensin (Ang)-(1-7) is an endogenous peptide hormone of the renin-angiotensin system which exerts diverse biological actions, some of them counterregulate Ang II effects. In the present study potential effect of Ang-(1-7) on phosphoinositide (PI) turnover was evaluated in neonatal rat brain. Cerebral cortex prisms of seven-day-old rats were preloaded with [(3)H]myoinositol, incubated with additions during 30 min and later [(3)H]inositol-phosphates (IPs) accumulation quantified.

Lisinopril as an antioxidant in hypertension?

Lisinopril is an inhibitor of the renin-angiotensin system. Does lisinopril minimize oxidative damage in spontaneously hypertensive rats (SHR) in comparison with the normotensive genetic controls Wistar Kyoto (WKY)? The authors note that lisinopril contained lipid peroxidation, elevated tissue glutathione levels, and influenced the activity of antioxidant enzymes such as catalase and glutathione peroxidase. Studies in humans testing the hypothesis that lisinopril has antioxidant function in vivo are warranted.

Behaviour of the anti-oxidant defence system and heme oxygenase-1 protein expression in fructose-hypertensive rats.

1. Addition of fructose to a rat diet for various periods of time leads to hypertension, hyperinsulinaemia and dyslipidaemia and provides a model for testing oxidative stress parameters in the animals. 2.

Hypothalamic cardiovascular effects of angiotensin-(1-7) in spontaneously hypertensive rats.

The objective of the present work was to study the cardiovascular actions of the intrahypothalamic injection of Ang-(1-7) and its effects on the pressor response to Ang II in spontaneously hypertensive (SH) rats and Wistar Kyoto (WKY) animals. In anaesthetized SH and WKY rats, a carotid artery was cannulated for mean arterial pressure (MAP) measurement and a stainless-steel needle was inserted into the anterior hypothalamus for drug administration. The cardiovascular effects of the intrahypothalamic administration of Ang-(1-7) were determined in SH and WKY rats.

Aortic coarctation induces oxidative stress in rat tissues.

The purpose of this study was to evaluate the induction of oxidative stress in heart and erythrocytes from rats with abdominal aorta coarctation (Coa) compared with sham-operated normotensive controls (Sham). The group of Coa animals developed myocardial hypertrophy, showing heart homogenates markedly increased levels of reduced glutathione (48%), lipid peroxidation (148%) and activation of superoxide dismutase and glutathione peroxidase (189% and 37%, respectively), compared with controls. Other oxidative stress indicators were also altered in erythrocytes from Coa rats: increased protein carbonyl content (141%) and total glutathione level (349%) were determined.

Synthesis and biological properties of chimeric interferon-alpha2b peptides.

We have previously reported the antiproliferative activity of synthetic sequences 29-35 and 122-139 of the interferon-alpha2b (IFN-alpha2b), both probably representing a common receptor recognition domain. In the search of new peptidic agonists, we designed and synthesized the linear peptide (Gly)2-122-137-Gly138-Gly29-30-35-(Gly)2, in which Gly residues replaced the 138 and 29 Cys bound through a disulfide bridge in the native cytokine. Additionally, a cyclic analog was obtained by reaction of the N- and C-terminal ends of the linear fragment.

Anterior hypothalamic beta-adrenoceptors in chronic aortic-coarctated hypertensive rats: an interaction with central angiotensin II receptors.

1. The aim of the present study was to investigate the activity of anterior hypothalamic beta-adrenoceptors and angiotensin (Ang) II receptors on blood pressure in normotensive rats and aortic-coarctated (ACo) animals at a chronic stage of hypertension. A possible interaction between beta-adrenoceptors and AngII pressor activity was also investigated.

Effects of angiotensin II type 1 receptor blockade on the oxidative stress in spontaneously hypertensive rat tissues.

The aim of this work was to investigate the production of oxidative damage in homogenized kidney, liver and brain of spontaneously hypertensive rats (SHR), as well as the involvement of angiotensin (Ang) II in this process. Groups of 12-week-old SHR and Wistar Kyoto rats (WKY) were given 10 mg/kg/day losartan in the drinking water during 14 days. Other groups of WKY and SHR without treatment were used as controls.

Endobain E, a brain Na+, K+ -ATPase inhibitor, decreases norepinephrine uptake in rat hypothalamus.

The ability of an endogenous brain Na+, K+ -ATPase inhibitor, termed endobain E, to increase [3H]norepinephrine release in rat hypothalamus was previously reported. Endobain E effect on neurotransmitter uptake was studied by assaying [3H]norepinephrine uptake in rat hypothalamus preparations, to observe uptake inhibition, which reached 60% with endobain E equivalent to 100 mg fresh cerebral cortex, an effect achieved with 40 or 400 microM ouabain. Results support the proposal that endobain E behaves as an ouabain-like substance.

Angiotensin-(1-7) inhibitory mechanism of norepinephrine release in hypertensive rats.

Release of norepinephrine (NE) by the hypothalamic nuclei may contribute to regulation of sympathetic nervous system (SNS) activity. Angiotensin-(1-7) [Ang-(1-7)] has an antihypertensive effect and may decrease SNS activity. We tested the hypothesis that Ang-(1-7) inhibits the release of NE in hypothalami, via the Ang-(1-7) and angiotensin II type 2 (AT2) receptors, acting through a bradykinin (BK)/NO-dependent mechanism.

Increased in vivo phosphorylation of insulin receptor at serine 994 in the liver of obese insulin-resistant Zucker rats.

Serine phosphorylation of the insulin receptor (IR) has been proposed to exert an inhibitory influence on its tyrosine kinase activity. Previous works using site-directed mutagenesis suggested that serine 994 of the IR (IR Ser 994) might be part of an inhibitory domain of the receptor. In this study we examined whether this residue is subjected to phosphorylation in vivo.