Angiotensin II receptor expression and relation to Helicobacter pylori-infection in the stomach of the Mongolian gerbil

<p>Abstract</p> <p>Background</p> <p>The role of the renin-angiotensin system in gastric physiology and disease has as yet been sparsely explored. The first aim of the study was to investigate the baseline presence and location of angiotensin II receptors (AT1R and AT2R) in the stomach of the Mongolian gerbil. A second aim was to elucidate whether the presence of <it>H. pylori </it>infection is associated with changes in the expression of these receptors.</p> <p>Methods</p> <p><it>H. pylori</it>-negative and <it>H. pylori-</it>infected (strain SS1 or TN2GF4) male Mongolian gerbils were investigated. The stomachs were examined at six or 12 months after inoculation by the use of immunohistochemistry, western blot and microscopic morphometry.</p> <p>Results</p> <p>AT1R and AT2R were located in a variety of cells in the gerbil gastric wall, including a subpopulation of endocrine cells in the antral mucosa and inflammatory cells infiltrating <it>H. pylori</it>-infected stomachs. Gerbils infected with the SS1 strain showed a significantly increased antral AT1R protein expression and an increased number of infiltrating polymorphonuclear leucocytes (PMNs) at 12 months. The AT1R protein expression correlated with the number of PMNs and the antral expression of myeloperoxidase.</p> <p>Conclusions</p> <p>Angiotensin II receptors are present in a variety of cells in the gastric wall of the Mongolian gerbil. The results indicate an influence dependent on the <it>H. pylori </it>strain on the gastric AT1R expression and a relationship between gastric AT1R expression and mucosal PMNs infiltration.</p

Angiotensin II AT\u3csub\u3e1\u3c/sub\u3e receptor blockade selectively enhances brain AT\u3csub\u3e2\u3c/sub\u3e receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats

Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT1 receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT1 receptor binding in the median eminence and basolateral amygdala, increased AT2 receptor binding in the medial subnucleus of the inferior olive, decreased AT2 binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT1 receptor blockade reduced AT1 receptor binding in all areas studied and enhanced AT2 receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT1 binding after stress, and prevented the stress-induced AT2 receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT1 blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT1 receptors, selectively increased central AT2 receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT1 and AT2 receptors in the regulation of the stress response, and the hypothesis that AT1 receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties. © 2008 Informa USA, Inc

Angiotensin II AT\u3csub\u3e1\u3c/sub\u3e and AT\u3csub\u3e2\u3c/sub\u3e receptor types regulate basal and stress-induced adrenomedullary catecholamine production through transcriptional regulation of tyrosine hydroxylase

The sympathoadrenal response to stress includes a profound increase in adrenomedullary catecholamine synthesis driven by stimulation of tyrosine hydroxylase (TH) transcription. We studied the role of Angiotensin II type 1 and 2 (AT1 and AT2) receptors during isolation stress, and under basal conditions. Pretreatment of rats with the AT1 receptor antagonist candesartan for 14 days prior to isolation completely prevented the stress-induced stimulation of catecholamine synthesis, decreasing tyrosine hydroxylase transcription by preventing the expression of the transcriptional factor, Fos-related antigen 2 (Fra-2). In addition, AT1 receptor antagonism prevented the stress-induced increase in adrenomedullary AT 2 receptor binding and protein. Treatment of non-stressed, grouped animals under basal conditions with the AT1 receptor or with PD 123319, an AT2 receptor antagonist, decreased the adrenomedullary norepinephrine (NE) content and TH transcription. While AT1 receptor antagonism decreased the levels of Fra-2 and the phosphorylated forms of cAMP responsive element binding protein (pCREB) and EKR2 (p-ERK2, phosphor-p42 MAP kinase), the AT2 antagonist decreased Fra-2 with no change in the phosphorylation of CREB or EKR2. Our results demonstrate that both adrenomedullary AT1 and AT2 receptor types maintain and promote the adrenomedullary catecholamine synthesis and the transcriptional regulation of TH. Instead of opposing effects, however, our results indicate a complex synergistic regulation between the AT1 and AT2 receptor types

Angiotensin II AT\u3csub\u3e1\u3c/sub\u3e receptor blockade prevents gastric ulcers during cold-restraint stress

Cold-restraint stress reduces gastric blood flow and produces acute gastric ulcers. We studied the role of Angiotensin II (Ang II) on gastric blood flow and gastric ulceration during stress. Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated for 14 days with the AT1 receptor antagonist candesartan before cold-restraint stress. AT1 blockade increased gastric blood flow 40% to 50%; prevented gastric ulcer formation by 70% to 80%; reduced the increase in adrenomedullary epinephrine and TH mRNA without preventing the stress-induced increase in adrenal corticosterone; decreased the stress-induced expression of tumor necrosis factor α (TNF-α) and adhesion protein ICAM-1 in arterial endothelium, and neutrophil infiltration in the gastric mucosa; and decreased PGE2 content. AT1 receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, anti-inflammatory effects with reduction in TNF-α, and ICAM-1 expression, leading to reduced neutrophil infiltration while maintaining the protective glucocorticoid effects and PGE2 release. Ang II has a crucial role, through stimulation of AT1 receptors, in the production and progression of stress-induced gastric injury, and AT1 receptor antagonists could be of therapeutic benefit

Brain angiotensin II, an important stress hormone: Regulatory sites and therapeutic opportunities

The presence of a brain Angiotensin II (Ang II) system, separated from and physiologically integrated with the peripheral, circulating renin-angiotensin system, is firmly established. Ang II is made in the brain and activates specific brain AT1 receptors to regulate thirst and fluid metabolism. Some AT1 receptors are located outside the blood-brain barrier and are sensitive to brain and circulating Ang II. Other AT1 receptors, located inside the blood-brain barrier, respond to stimulation by Ang II of brain origin. AT1 receptors in the subfornical organ, the hypothalamic paraventricular nucleus (PVN), and the median eminence are involved in the regulation of the stress response. In particular, AT1 receptors in the PVN are under glucocorticoid control and regulate corticotrophin-releasing hormone (CRH) formation and release. In the PVN, restraint elicits a fast increase in AT1 receptor mRNA expression. The expression of paraventricular AT1 receptors is increased during repeated restraint and after 24 h of isolation stress, and their stimulation is essential for the hypothalamic-pituitary-adrenal axis activation, the hallmark of the stress response. Peripheral administration of an AT1 receptor antagonist blocks peripheral and brain AT1 receptors, prevents the sympathoadrenal and hormonal response to isolation stress, and prevents the gastric stress ulcers that are a characteristic consequence of cold-restraint stress. This evidence indicates that pharmacologic inhibition of the peripheral and brain Ang II system by AT1 receptor blockade has a place in the prevention and treatment of stress-related disorders

A previous history of repeated amphetamine exposure modifies brain angiotensin II AT1 receptor functionality

Previous results from our laboratory showed that angiotensin II AT1 receptors (AT1-R) are involved in the neuroadaptative changes induced by amphetamine. The aim of the present work was to study functional and neurochemical responses to angiotensin II (ANG II) mediated by AT1-R activation in animals previously exposed to amphetamine. For this purpose male Wistar rats (250–320 g) were treated with amphetamine (2.5 mg/kg/day intraperitoneal) or saline for 5 days and implanted with intracerebroventricular (i.c.v.) cannulae. Seven days after the last amphetamine administration the animals received ANG II (400 pmol) i.c.v. One group was tested in a free choice paradigm for sodium (2% NaCl) and water intake and sacrificed for Fos immunoreactivity (Fos-IR) determinations. In a second group of rats, urine and plasma samples were collected for electrolytes and plasma renin activity determination and then they were sacrificed for Fos-IR determination in Oxytocinergic neurons (Fos-OT-IR). Results: Repeated amphetamine exposure (a) prevented the increase in sodium intake and Fos-IR cells in caudate-putamen and accumbens nucleus induced by ANG II i.c.v. (b) potentiated urinary sodium excretion and Fos-OT-IR in hypothalamus and (c) increased the inhibitory response in plasma renin activity, in response to ANG II i.c.v. Our results indicate a possible functional desensitisation of AT1-R in response to ANG II, induced by repeated amphetamine exposure. This functional AT1-R desensitisation allows to unmask the effects of ANG II i.c.v. mediated by oxytocin. We conclude that the long lasting changes in brain AT1-R functionality should be considered among the psychostimulant-induced neuroadaptations.Fil: Casarsa, Brenda Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Marinzalda, María de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Marchese, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Paz, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Vivas, Laura Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra; ArgentinaFil: Bregonzio, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Baiardi, Gustavo Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Gaseous products and secondary organic aerosol formation during long term oxidation of isoprene and methacrolein

International audienceFirst-and higher order-generation products formed from the oxidation of isoprene and methacrolein with OH radicals in the presence of NOx have been studied in a simulation chamber. Significant oxidation rates have been maintained for up to 7 h, allowing the study of highly oxidized products. Gas-phase product distribution and yields were obtained, and show good agreement with previous studies. Secondary organic aerosol (SOA) formation has also been investigated. SOA mass yields from previous studies show large discrepancies. The mass yields obtained here were consistent with the lowest values found in the literature, and more specifically in agreement with studies carried out with natural light or artificial lamps with emission similar to the solar spectrum. Differences in light source are therefore proposed to explain partially the discrepancies observed between different studies in the literature for both isoprene and methacrolein-SOA mass yields. There is a high degree of similarity between the SOA mass spectra from isoprene and methacrolein photooxidation, thus strengthening the importance of the role of methacrolein in SOA formation from isoprene photooxidation under our experimental conditions (i.e., presence of NOx and long term oxidation). According to our results, SOA mass yields from both isoprene and methacrolein in the atmosphere could be lower than suggested by most of the current chamber studies