Hypothalamic gene expression in w-3 PUFA-deficient male rats before, and following, development of hypertension

Dietary deficiency of ω-3 fatty acids (ω-3 DEF) produces hypertension in later life. This study examined the effect of ω-3 DEF on blood pressure and hypothalamic gene expression in young rats, before the development of hypertension, and in older rats following the onset of hypertension. Animals were fed experimental diets that were deficient in ω-3 fatty acids, sufficient in short-chain ω-3 fatty acids or sufficient in short- and long-chain ω-3 fatty acids, from the prenatal period until 10 or 36 weeks-of-age. There was no difference in blood pressure between groups at 10 weeks-of-age; however, at 36 weeks-of-age ω-3 DEF animals were hypertensive in relation to sufficient groups. At 10 weeks, expression of angiotensin-II1A receptors and dopamine D3 receptors were significantly increased in the hypothalamic tissue of ω-3 DEF animals. In contrast, at 36 weeks, α2a and β1 adrenergic receptor expression was significantly reduced in the ω-3 DEF group. Brain docosahexaenoic acid was significantly lower in ω-3 DEF group compared with sufficient groups. This study demonstrates that dietary ω-3 DEF causes changes both in the expression of key genes involved in central blood pressure regulation and in blood pressure. The data may indicate that hypertension resulting from ω-3 DEF is mediated by the central adrenergic system.

Venous tone and cardiac function in the South American rattlesnake Crotalus durissus: mean circulatory filling pressure during adrenergic stimulation in anaesthetised and fully recovered animals

The effects of adrenergic stimulation on mean circulatory filling pressure (MCFP), central venous pressure (P-CV) and stroke volume (Vs), as well as the effects of altered MCFP through changes of blood volume were investigated in rattlesnakes (Crotalus durissus). MCFP is an estimate of the upstream pressure driving blood towards the heart and is determined by blood volume and the activity of the smooth muscle cells in the veins (venous tone). MCFP can be determined as the plateau in P-CV during a total occlusion of blood flow from the heart.Vs decreased significantly when MCFP was lowered by reducing blood volume in anaesthetised snakes, whereas increased MCFP through infusion of blood (up to 3 ml kg(-1)) only led to a small rise in Vs. Thus, it seems that end-diastolic volume is not affected by an elevated MCFP in rattlesnakes. To investigate adrenergic regulation on venous tone, adrenaline as well as phenylephrine and isoproterenol (alpha- and beta-adrenergic agonists, respectively) were infused as bolus injections (2 and 10 mu g kg(-1)). Adrenaline and phenylephrine caused large increases in MCFP and P-CV, whereas isoproterenol decreased both parameters. This was also the case in fully recovered snakes. Therefore, adrenaline affects venous tone through both alpha- and beta-adrenergic receptors, but the alpha-adrenergic receptor dominates at the dosages used in the present study. Injection of the nitric oxide donor SNP caused a significant decrease in P-CV and MCFP. Thus, nitric oxide seems to affect venous tone.

Role of nitric oxide and beta-adrenoceptors of the central nervous system on the salivary flow induced by pilocarpine injection into the lateral ventricle

Our studies have focused on the effect of L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and L-arginine, the substrate of NOS, on salivary secretion induced by the administration of pilocarpine into the lateral cerebral ventricle (LV) of rats. The present study has also investigated the role of the beta-adrenergic agonists and antagonist injected into LV on the salivary secretion elicited by the injection of pilocarpine into LV. Male Holtzmann rats with a stainless-steel cannula implanted into the LV were used. The amount of salivary secretion was studied over a 7-min period after injection of pilocarpine, isoproterenol, propranolol, salbutamol, salmeterol, L-NAME and L-arginine. The injection of pilocarpine (10, 20, 40, 80 and 160 mug/mul) into LV produced a dose-dependent increase in salivary secretion. The injection of L-NAME (40 mug/mul) into LV alone produced an increase in salivary secretion. The injection of L-NAME into LV previous to the injection of pilocarpine produced an increase in salivary secretion. L-Arginine (30 mug/mul) injected alone into LV produced no change in salivary secretion. L-Arginine injected into LV attenuated pilocarpine-induced salivary secretion. The isoproterenol (40 nmol/mul) injected into LV increased into LV increased the salivary secretion. When injected previous to pilocarpine at a dose of 20 and 40 mug/mul, isoproterenol produced and additive effect on pilocarpine-induced salivary secretion. The 40-nmol/mul dose of propranolol injected alone or previous to pilocarpine into LV attenuated the pilocarpine-induced salivary secretion. The injection of salbutamol (40 nmol/mul), a specific beta-2 agonist, injected alone into LV produced no change in salivary secretion and when injected previous to pilocarpine produced and increase in salivary secretion. The 40-nmol/mul dose of salmeterol, a long-acting beta-2 agonist, injected into LV alone or previous to pilocarpine produced no change in salivary secretion. The results have shown that central injections of L-NAME and L-arginine interfere with the salivary secretion, which implies that might participate in pilocarpine-induced salivary secretion. The interaction between cholinergic and beta-adrenergic receptors of the central nervous system (CNS) for the control of salivary secretion can also be postulated. (C) 2002 Elsevier B.V. All rights reserved.

Interaction between paraventricular nucleus and medial septal area on the renal effects induced by adrenaline

The aim of the present study was to analyze the role of alpha(1),alpha(2)-adrenoceptors, and the effects of losartan and PD123319 (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) injected into the paraventricular nucleus (PVN) on the diuresis, natriuresis, and kaliuresis induced by administration of adrenaline into the medial septal area (MSA). Male Holtzman rats with a stainless steel cannula implanted into the MSA and bilaterally into the PVN were used. The administration of adrenaline into the MSA increased in a dose-dependent manner the urine, sodium, and potassium excretions. The previous administration of prazosin (an alpha(1)-adrenoceptor antagonist) injected into the PVN abolished the above effects of adrenaline, whereas yohimbine (an a-adrenoceptor antagonist) doesn't affect the diuresis, natriuresis, and kaliuresis induced by adrenaline. Pretreatment with losartan into the PVN decreased in a dose-dependent manner the urine, sodium, and potassium excretions induced by MSA administration of adrenaline (50 ng), while PVN PD123319 was without effect. These results indicate that urinary and electrolyte excretion effects induced by adrenaline into the MSA are mediated primarily by PVN AT, receptors. However, the doses of losartan were more effective when combined with the doses of PD123319 than given alone, suggesting that the urinary, natriuretic, and kaliuretic effects of MSA adrenaline may involve activation of multiple angiotensin II receptors subtypes into the PVN. (C) 2004 Elsevier B.V All rights reserved.

Medial septal area ANG II receptor subtypes in the regulation of urine and sodium excretion induced by vasopressin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of renin-angiotensin system signalling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Gill chemoreceptors and cardio-respiratory reflexes in the neotropical teleost pacu, Piaractus mesopotamicus

This study examined the location and distribution of O-2 chemoreceptors involved in cardio-respiratory responses to hypoxia in the neotropical teleost, the pacu (Piaractus mesopotamicus). Intact fish and fish experiencing progressive gill denervation by selective transection of cranial nerves IX and X were exposed to gradual hypoxia and submitted to intrabuccal and intravenous injections of NaCN while their heart rate, ventilation rate and ventilation amplitude were measured. The chemoreceptors producing reflex bradycardia were confined to, but distributed along all gill arches, and were sensitive to O-2 levels in the water and the blood. Ventilatory responses to all stimuli, though modified, continued following gill denervation, however, indicating the presence of internally and externally oriented receptors along all gill arches and either in the pseudobranch or at extra-branchial sites. Chemoreceptors located on the first pair of gill arches and innervated by the glossopharyngeal nerve appeared to attenuate the cardiac and respiratory responses to hypoxia. The data indicate that the location and distribution of cardio-respiratory O-2 receptors are not identical to those in tambaqui (Colossoma macropomum) despite their similar habitats and close phylogenetic lineage, although the differences between the two species could reduce to nothing more than the presence or absence of the pseudobranch.

Recent developments for smoking cessation and treatment of nicotine dependence

Nicotine is an addictive drug like heroin, amphetamine or cocaine. Addiction to tobacco leads to significant failure rates in programmes for smoking cessation. The alpha(4)beta(2) and alpha(7) nicotinic acetylcholine receptors (nAChRs) and CB1 cannabinoid receptors play an important role in nicotine addiction.

Medial Septal Area Vasopressin Receptor Subtypes in the Regulation of Urine and Sodium Excretion in Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Progesterone (PR), Oestrogen (ER-alpha and ER-beta) and Oxytocin (OTR) Gene Expression in the Oviduct and Uterus of Pregnant and Non-pregnant Bitches

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study of the contraction induced by norepinephrine and clonidine in the isolated guinea-pig ileum

Norepinephrine (NE) and clonidine produce a phasic, dose-dependent contraction of the isolated guinea-pig terminal ileum. The effect of NE was blocked by prazosin which produced a parallel rightward shift of the concentration-effect curve to NE, with a significant depression of maximum effects. Yohimbine and indomethacin noncompetitively blocked, whereas practolol potentiated, the contractile effect of NE. The contractile effect of clonidine was not antagonized by indomethacin or atropine. These results suggest that the isolated guinea-pig terminal ileum has excitatory receptors sensitive to clonidine stimulation and excitatory alpha receptors sensitive to blockade by prazosin, and that the activation of the latter may be related to the activation of endogenous prostaglandin synthesis.

Niobium filtration of conventional and high-frequency x-ray generator beams for intraoral radiography. Effects on absorbed doses, image density and contrast, and photon spectra

We have studied the effects of niobium beam filtration on absorbed doses, on image density and contrast, and on photon spectra with conventional and high-frequency dental x-ray generators. Added niobium reduced entry and superficial absorbed doses in periapical radiography by 9% to 40% with film and digital image receptors, decreased the radiation necessary to produce a given image density on E-speed film and reduced image contrast on D- and E-speed films. As shown by increased half-value layers for aluminum, titanium, and copper and by pulse-height analyses of beam spectra, niobium increased average beam energy by 6% to 19%. Despite the benefits of adding niobium on patient dose reduction and on narrowing the beams' energy spectra, the beam can be overhardened. Adding niobium, therefore, strikes the best balance between radiation dose reduction and beam attenuation, with its risks of increased exposure times, motion blur, and diminished image contrast, when it is used at modest thicknesses (30 μm) and at lower kVp (70) settings. © 1995 Mosby-Year Book, Inc.

Cytokines profile and clinical-metabolic alterations in HIV-1-infected individuals with and without lypodistrophy

Highly active antiretroviral therapy (HAART) has lead to a dramatic decrease in the morbidity of patients infected with HIV. However, metabolic side effects, including lipodystrophy and dyslipidemia, have been reported in patients treated with antiretroviral therapy (HAART). The aim of this study was to analyze the clinical and metabolic alterations and the cytokines TNF-α, IFN-γ, IL-2, IL-10 and TNF-II receptors profile in the serum of treated HIV-1-infected individuals with or without lipodystrophy. Eighty-four adult patients were analyzed, 42 females and 42 males, their mean age was 37 years old, and they received HAART for at least 15 months. These patients were ambulatory outpatients from the Infectious and Parasitary Disease Area of Botucatu School of Medicine, UNESP. Subsequently the individuals were distributed into 2 groups, G1: 42 HIV-infected individuals with lipodystrophy, and G2: 42 HIV-infected individuals without lipodystrophy. Among the antiretrovirals used, stavudine was more associated to the lipodystrophy group and zidovudine to the group without lipodystrophy. CD4, CD8, viral load, glucose, albumin, and the circulating lipid did not present any difference in the group comparison, except for triglyceride that was elevated in the lipodystrophy group and HDL which was present in low concentration in more patients of G1. The cytokines TNF-α, TNF-RII, and IL-10 profile presented high levels in the lipodystrophy group; also it was positively correlated with this group. On the other hand, IL-2 and IFN-γ presented low levels in this group. High levels of TNF-α and its receptor seem to be associated to the development of lipodystrophy in patients receiving HAART.

Paraventricular nucleus of the hypothalamus glutamate neurotransmission modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats

In the present study, the involvement of paraventricular nucleus of the hypothalamus (PVN) glutamate receptors in the modulation of autonomic (arterial blood pressure, heart rate and tail skin temperature) and neuroendocrine (plasma corticosterone) responses and behavioral consequences evoked by the acute restraint stress in rats was investigated. The bilateral microinjection of the selective non-NMDA glutamate receptor antagonist NBQX (2 nmol/ 100 nL) into the PVN reduced the arterial pressure increase as well as the fall in the tail cutaneous temperature induced by the restraint stress, without affecting the stress-induced tachycardiac response. On the other hand, the pretreatment of the PVN with the selective NMDA glutamate receptor antagonist LY235959 (2 nmol/100 nL) was able to increase the stress-evoked pressor and tachycardiac response, without affecting the fall in the cutaneous tail temperature. The treatment of the PVN with LY235959 also reduced the increase in plasma corticosterone levels during stress and inhibited the anxiogenic-like effect observed in the elevated plus-maze 24 h after the restraint session. The present results show that NMDA and non-NMDA receptors in the PVN differently modulate responses associated to stress. The PVN glutamate neurotransmission, via non-NMDA receptors, has a facilitatory influence on stress-evoked autonomic responses. On the other hand, the present data point to an inhibitory role of PVN NMDA receptors on the cardiovascular responses to stress. Moreover, our findings also indicate an involvement of PVN NMDA glutamate receptors in the mediation of the plasma corticosterone response as well as in the delayed emotional consequences induced by the restraint stress. © 2012 Elsevier B.V. and ECNP.

Regulation of visfatin by microbial and biomechanical signals in PDL cells

Objectives: This in vitro study was established to examine whether visfatin thought to be a link between periodontitis and obesity is produced by periodontal ligament (PDL) cells and, if so, whether its synthesis is modulated by microbial and/or biomechanical signals. Materials and methods: PDL cells seeded on BioFlex® plates were exposed to the oral pathogen Fusobacterium nucleatum ATCC 25586 and/or subjected to biomechanical strain for up to 3 days. Gene expression of visfatin and toll-like receptors (TLR) 2 and 4 was analyzed by RT-PCR, visfatin protein synthesis by ELISA and immunocytochemistry, and NFκB nuclear translocation by immunofluorescence. Results: F. nucleatum upregulated the visfatin expression in a dose- and time-dependent fashion. Preincubation with neutralizing antibodies against TLR2 and TLR4 caused a significant inhibition of the F. nucleatum-upregulated visfatin expression at 1 day. F. nucleatum stimulated the NFκB nuclear translocation. Biomechanical loading reduced the stimulatory effects of F. nucleatum on visfatin expression at 1 and 3 days and also abrogated the F. nucleatum-induced NFκB nuclear translocation at 60 min. Biomechanical loading inhibited significantly the expression of TLR2 and TLR4 at 3 days. The regulatory effects of F. nucleatum and/or biomechanical loading on visfatin expression were also observed at protein level. Conclusions: PDL cells produce visfatin, and this production is enhanced by F. nucleatum. Biomechanical loading seems to be protective against the effects of F. nucleatum on visfatin expression. Clinical relevance: Visfatin produced by periodontal tissues could play a major role in the pathogenesis of periodontitis and the interactions with obesity and other systemic diseases. © 2013 Springer-Verlag Berlin Heidelberg.