Gustavo Baiardi

Catholic University of Córdoba, Córdoba, Córdoba, Argentina

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Publications (18)53.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 (250-320g) were treated with amphetamine (2.5mg/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 (400pmol) 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 immunoreactivity determination in Oxytocinergic neurons (Fos-OT-IR). 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 desensitization of AT1-R in response to ANG II, induced by repeated amphetamine exposure. This functional AT1-R desensitization 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. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 08/2015; 307. DOI:10.1016/j.neuroscience.2015.08.027 · 3.36 Impact Factor
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    ABSTRACT: A single or repeated exposure to psychostimulants induces long-lasting neuroadaptative changes. Different neurotransmitter systems are involved in these responses including the neuropeptide angiotensin II. Our study tested the hypothesis that the neuroadaptative changes induced by amphetamine produce alterations in brain RAS components that are involved in the expression of the locomotor sensitization to the psychostimulant drug. Wistar male rats, pretreated with amphetamine were used 7 or 21 days later to study AT1 receptors by immunohistochemistry and western blot and also angiotensinogen mRNA and protein in caudate putamen and nucleus accumbens. A second group of animals was used to explore the possible role of Ang II AT1 receptors in the expression of behavioral sensitization. In these animals treated in the same way, bearing intra-cerebral cannula, the locomotor activity was tested 21 days later, after an amphetamine challenge injection and the animals received an AT1 blocker, losartan, or saline 5min before the amphetamine challenge. An increase of AT1 receptor density induced by amphetamine was found in both studied areas and a decrease in angiotensinogen mRNA and protein only in CPu at 21 days after treatment; meanwhile, no changes were established in NAcc. Finally, the increased locomotor activity induced by amphetamine challenge was blunted by losartan administration in CPu. No differences were detected in the behavioral sensitization when the AT1 blocker was injected in NAcc. Our results support the hypothesis of a key role of brain RAS in the neuroadaptative changes induced by amphetamine.
    Behavioural Brain Research 07/2014; 272. DOI:10.1016/j.bbr.2014.07.021 · 3.03 Impact Factor
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    ABSTRACT: Central nucleus of the amygdala (CeA) is one of the most important regulatory centres for the emotional processes. Among the different neurotransmitter systems present in this nucleus, AT1 receptors have been also found, but their role in the generation and modulation of emotions is not fully understood. The present work evaluated the effect of intra-amygdalar injection of losartan (AT1 receptor antagonist) and angiotensin II (Ang II) in the anxiety state induced by fear-potentiated plus maze in male Wistar rats. Fear in the elevated plus maze can be potentiated by prior inescapable footshock stress. The decrease in the time spent in the open arms induced by the inescapable footshock was totally prevented by losartan (4 pmol) administration in CeA. It was also found that Ang II (48 fmol) administration decreased the time spent in the open arms in animals with or without previous footshock exposure. The locomotor activity and grooming behaviour were also evaluated. The results obtained from the different parameters analyzed allowed us to conclude that the Ang II AT1 receptors in CeA are involved in the anxiety state induced by stress in the fear-potentiated plus-maze behaviour.
    BioMed Research International 06/2014; 2014(2):183248. DOI:10.1155/2014/183248 · 1.58 Impact Factor
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    ABSTRACT: Background: The effect of the agonism on γ-aminobutyric acid (GABA) receptors was studied within medial prefrontal cortex (mPFC), amygdala (AMY) and ventral hipocampus (VH) in the plus-maze test in male rats bilaterally cannulated. These structures send glutamatergic projections to the nucleus accumbens septi (NAS), in which interaction and integration between these afferent pathways has been described. In a previous study of our group, blockade of glutamatergic transmission within NAS induced an anxiolytic like effect. Methods: Three rat groups received either saline or dipotassium chlorazepate (1 or 2 μg/1 μl solution) 15 min before testing. Time spent in the open arms (TSOA), time per entry (TPE), extreme arrivals (EA), open and closed arms entries (OAE, CAE) and relationship between open- and closed-arms quotient (OCAQ) were recorded. Results: In the AMY injected group TSOA, OAE and EA were increased by the higher doses of dipotassium chlorazepate (p < 0.01). In the mPFC, TPE was decreased by both doses (p < 0.05). Injection within ventral hippocampus (VH) decreased TSOA, OAE and OCAQ with lower doses (p < 0.05). When the three studied saline groups were compared, TSOA, OAE, EA and OCAQ were enhanced in the VH group when compared to mPFC and AMY (p < 0.001). Insertion of inner canula (p < 0.001, p < 0.01, p < 0.01) and saline injection showed an increasing significant difference (p < 0.001 in all cases) with the action of guide cannula alone within VH in TSOA, OAE and EA. Conclusion: We conclude that the injection of dipotassium chlorazepate has a differential effect depending of the brain area, leading to facilitatory and inhibitory effects on anxiety processing.
    Pharmacological reports: PR 05/2013; 65(3):566-78. DOI:10.1016/S1734-1140(13)71034-X · 1.93 Impact Factor
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    ABSTRACT: It has been recognized that the stress-related peptides are involved in anxiety states. Angiotensin II receptor blockade by systemic administration of the AT(1) receptor antagonists has been proposed as a new treatment possibility for anxiety disorders. For better understanding of the related mechanisms, in this study we evaluated effects of bilateral intraamygdaloid injections of 2 (LOS 2) and 4 (LOS 4) μg of losartan (LOS), a selective AT(1) receptor antagonist, on the behavior of the not stressed and acutely stressed rats in an elevated "plus" maze. Under non-stress conditions, LOS 4 increased time spent in the open arms (p < 0.01), number of extreme open arm arrivals (p < 0.05), time per entry (p < 0.01), and the number of total arm entries (p < 0.05) showing thus considerable anxiolytic activity. The open arm extreme arrivals were increased by LOS 4 in both not stressed (p < 0.05) and stressed (p < 0.05) rats. When no stressed and stressed LOS 4 animals were compared, time per entry and the number of closed arm entries (p < 0.05, both) were decreased in the latter group. Moreover, the LOS 4 stressed rats had significantly increased open/closed arm quotient (p < 0.05) as compared to the both control and LOS 4 non-stress group (p < 0.05, both). These findings suggest that the AT(1) receptor blockade in amygdala is important for the anxiolytic action of LOS (and probably other AT(1) receptor blockers) under both non-stress and stress conditions.
    Pharmacological reports: PR 01/2012; 64(1):54-63. DOI:10.1016/S1734-1140(12)70730-2 · 1.93 Impact Factor
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    ABSTRACT: The amygdaloid complex is involved in anxiety or fear responses to stressful stimuli. In this study the effect of neuropeptide-EI on anxiety-like behavior and its influence on adrenocortical function was tested in male Wistar rats that were injected bilaterally in the basolateral amygdala with neuropeptide-EI (1 μg/1 μl) or artificial cerebrospinal fluid and placed on the plus maze. The plasma corticosterone levels were analyzed in controls and plus-maze exposed animals. Neuropeptide-EI in the basolateral amygdala significantly decreased the time spent in open arms but had no effect on locomotor activity, showing an anxiogenic effect. However, neuropeptide administration did not change serum corticosterone levels compared with vehicle controls. Our results suggest that the anxiogenic effect of neuropeptide-EI could be independent of the hypothalamic-pituitary-adrenocortical system response.
    Neuroreport 12/2010; 22(2):83-7. DOI:10.1097/WNR.0b013e328342b9ef · 1.52 Impact Factor
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    ABSTRACT: We studied the effect of ovariectomy and estrogen replacement on expression of adrenal angiotensin II AT1 and AT2 receptors, aldosterone content, catecholamine synthesis, and the transcription factor Fos-related antigen 2 (Fra-2). Ovariectomy increased AT1 receptor expression in the adrenal zona glomerulosa and medulla, and decreased adrenomedullary catecholamine content and Fra-2 expression when compared to intact female rats. In the zona glomerulosa, estrogen replacement normalized AT1 receptor expression, decreased AT1B receptor mRNA, and increased AT2 receptor expression and mRNA. Estrogen treatment decreased adrenal aldosterone content. In the adrenal medulla, the effects of estrogen replacement were: normalized AT1 receptor expression, increased AT2 receptor expression, AT2 receptor mRNA, and tyrosine hydroxylase mRNA, and normalized Fra-2 expression and catecholamine content. We demonstrate that the constitutive adrenal expression of AT1 receptors, catecholamine synthesis and Fra-2 expression are partially under the control of reproductive hormones. Our results suggest that estrogen treatment decreases aldosterone production through AT1 receptor downregulation and AT2 receptor upregulation. AT2 receptor upregulation and modulation of Fra-2 expression may participate in the estrogen-dependent normalization of adrenomedullary catecholamine synthesis in ovariectomized rats. The AT2 receptor upregulation and the decrease in AT1 receptor function and in the production of the fluid-retentive, pro-inflammatory hormone aldosterone partially explain the protective effects of estrogen therapy.
    Neuroendocrinology 09/2008; 88(4):276-86. DOI:10.1159/000150977 · 4.37 Impact Factor
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    ABSTRACT: Excessive grooming behaviour is induced by intracerebroventricular injections of the neuropeptide glutamic acid isoleucine amide (neuropeptide-EI), via the activation of A-10 dopaminergic neurons and the noradrenergic system. Our object was to study the latter system involved in these behaviours, using male Wistar rats weighing 250-300 g with i.c.v. implants. The results show that all the adrenoceptor antagonists "per se" do not affect excessive grooming behaviour or motor activity. Intracerebroventricular administration of propranolol, a general beta-adrenoceptor antagonist, before neuropeptide-EI, inhibited the induced excessive grooming behaviour in a dose dependent manner. Metoprolol, a beta(1)-adrenoceptor antagonist, also blocked this behaviour. However, intracerebroventricular injections of phentolamine, an alpha-adrenoceptor antagonist, and ((+/-)-1-[2,3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol), a beta(2)-adrenoceptor antagonist, had no effect on the behaviour induced by neuropeptide-EI induced behaviour for any of the doses tested. On the other hand, isoproterenol, a general beta-adrenoceptor agonist and dobutamine, a beta(1)-adrenoceptor agonist, both elicited similar behaviours as those induced by neuropeptide-EI. These results support the hypothesis that a relationship exists between neuropeptide-EI and beta-adrenoceptors, more specifically the beta(1)-adrenoceptor, as found with other similar endogenous peptides such as neurotensin, cholecystin, substance P and alpha-melanocyte stimulating hormone. Hence, neuropeptide-EI could probably be exerting a neuromodulating effect on the central nervous system.
    European Journal of Pharmacology 08/2007; 568(1-3):186-91. DOI:10.1016/j.ejphar.2007.04.024 · 2.53 Impact Factor
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    ABSTRACT: Effects of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA glutamatergic receptors on performance in the hole board test was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats, divided into 5 groups, received either 1 microl injections of saline, (+/-) 2-amino-7-phosphonoheptanoic acid (AP-7) (0.5 or 1 microg) or 2,3-dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.5 or 1 microg) 10 min before testing. An increase by AP-7 was observed in ambulatory movements (0.5 microg; p < 0.05), non-ambulatory movements and number of movements (1 microg; p < 0.05); sniffing and total exploration (1 microg; p < 0.01). When holes were considered in order from the first to the fifth by the number of explorations, the most visited holes (first and second) of the AP-7 group were significantly higher than the corresponding holes of saline group (p < 0.05 for 0.5 microg and p < 0.001 for 1 microg). When the second hole was compared with the first of his group, a difference was only observed in the AP-7 1 microg group (p < 0.001). Increasing differences between the other holes and the first were observed by drug treatment. At molecular level, it was observed that AP-7 induced an increase of the coat protein AP-2 expression in Acc, but not AP-180 neither the synaptic protein synaptophysin. The increase of AP-2 was also observed in the medial prefrontal cortex by the action of AP-7 but not NBQX. We conclude that NMDA glutamatergic blockade might induce an activation of the endocytic machinery into the Acc, leading to stereotypies and perseverations, lacking cortical intentional direction.
    Journal of Neural Transmission 02/2007; 114(12):1519-28. DOI:10.1007/s00702-007-0776-7 · 2.40 Impact Factor
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    ABSTRACT: The brain and the peripheral (hormonal) angiotensin II systems are stimulated during stress. Activation of brain angiotensin II AT(1) receptors is required for the stress-induced hormone secretion, including CRH, ACTH, corticoids and vasopressin, and for stimulation of the central sympathetic activity. Long-term peripheral administration of the angiotensin II AT(1) antagonist candesartan blocks not only peripheral but also brain AT(1) receptors, prevents the hormonal and sympathoadrenal response to isolation stress and prevents the formation of stress-induced gastric ulcers. The mechanisms responsible for the prevention of stress-induced ulcers by the AT(1) receptor antagonist include protection from the stress-induced ischemia and inflammation (neutrophil infiltration and increase in ICAM-1 and TNF-alpha) in the gastric mucosa and a partial blockade of the stress-induced sympathoadrenal stimulation, while the protective effect of the glucocorticoid release during stress is maintained. AT(1) receptor antagonism prevents the stress-induced decrease in cortical CRH(1) and benzodiazepine binding and is anxiolytic. Blockade of brain angiotensin II AT(1) receptors offers a novel therapeutic opportunity for the treatment of anxiety and other stress-related disorders.
    Regulatory Peptides 07/2005; 128(3):227-38. DOI:10.1016/j.regpep.2004.12.015 · 1.83 Impact Factor
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    ABSTRACT: We studied renal AT1 and AT2 receptors in male, female, ovariectomized and ovariectomized-estrogen-treated Wistar-Hanover and Wistar-Kyoto rats. AT1 receptors and AT1A receptor mRNA predominated, with no significant differences between males and females. AT2 receptor expression was restricted in female rats to the capsule, the transition zone between outer and inner medulla, the endothelium lining the papilla, and arcuate arteries and veins. There were no AT2 receptors in male rats, while male mice express substantial numbers of estrogen-dependent AT2 receptors. Arcuate arteries and veins expressed AT1B mRNA in males and females, and AT2 mRNA in females only. AT1 receptor and AT2 receptor expression were estrogen-dependent, with increases in AT1 and AT2 receptor expression after estrogen treatment in ovariectomized rats. Estrogen treatment increased prostaglandin E2 (PGE2) and cGMP concentrations in the renal medulla, and eNOS expression in cortical arteries. In rodents, expression of renal Angiotensin II receptor types is estrogen-dependent, with significant species, strain and area differences. Our results support an important role for AT2 receptors in the regulation of renal function and in the protective effects of estrogen in the kidney.
    Regulatory Peptides 02/2005; 124(1-3):7-17. DOI:10.1016/j.regpep.2004.06.021 · 1.83 Impact Factor
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    ABSTRACT: Peripheral and brain angiotensin II AT(1) receptor blockade decreases high blood pressure, stress, and neuronal injury. To clarify the effects of long-term brain Ang II receptor blockade, the AT(1) blocker, candesartan, was orally administered to spontaneously hypertensive rats (SHRs) for 40 days, followed by intraventricular injection of 25 ng of Ang II. Before Ang II injection, AT(1) receptor blockade normalized blood pressure and decreased plasma adrenocorticotropic hormone (ACTH) and corticosterone. After central administration of excess Ang II, the reduction of ACTH and corticosterone release induced by AT(1) receptor blockade no longer occurred. Central Ang II administration to vehicle-treated SHRs further increased blood pressure, provoked drinking, increased tyrosine hydroxylase (TH) mRNA expression in the locus coeruleus, and stimulated sympathoadrenal catecholamine release. Pretreatment with the AT(1) receptor antagonist eliminated Ang II-induced increases in blood pressure, water intake, and sympathoadrenal catecholamine release; inhibited peripheral and brain AT(1) receptors; increased AT(2) receptor binding in the locus coeruleus, inferior olive, and adrenal cortex; and decreased AT(2) receptor binding in the adrenal medulla. Inhibition of brain AT(1) receptors correlated with decreased TH transcription in the locus coeruleus, indicating a decreased central sympathetic drive. This, and the diminished adrenomedullary AT(1) and AT(2) receptor stimulation, result in decreased sympathoadrenomedullary stimulation. Oral administration of AT(1) antagonists can effectively block central actions of Ang II, regulating blood pressure and reaction to stress, and selectively and differentially modulating sympathoadrenal response and the hypothalamic-pituitary-adrenal stimulation produced by brain Ang II--effects of potential therapeutic importance.
    Brain Research 12/2004; 1028(1):9-18. DOI:10.1016/j.brainres.2004.06.079 · 2.84 Impact Factor
  • J M Saavedra · H Ando · I Armando · G Baiardi · C Bregonzio · M Jezova · J Zhou ·
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    ABSTRACT: 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 AT(1) receptors to regulate thirst and fluid metabolism. Some AT(1) receptors are located outside the blood-brain barrier and are sensitive to brain and circulating Ang II. Other AT(1) receptors, located inside the blood-brain barrier, respond to stimulation by Ang II of brain origin. AT(1) 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, AT(1) 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 AT(1) receptor mRNA expression. The expression of paraventricular AT(1) 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 AT(1) receptor antagonist blocks peripheral and brain AT(1) 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 AT(1) receptor blockade has a place in the prevention and treatment of stress-related disorders.
    Annals of the New York Academy of Sciences 07/2004; 1018(1):76-84. DOI:10.1196/annals.1296.009 · 4.38 Impact Factor
  • I Armando · M Jezova · C Bregonzio · G Baiardi · J M Saavedra ·
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    ABSTRACT: 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 (AT(1) and AT(2)) receptors during isolation stress, and under basal conditions. Pretreatment of rats with the AT(1) 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, AT(1) 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 AT(1) receptor or with PD 123319, an AT(2) receptor antagonist, decreased the adrenomedullary norepinephrine (NE) content and TH transcription. While AT(1) 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 AT(2) antagonist decreased Fra-2 with no change in the phosphorylation of CREB or EKR2. Our results demonstrate that both adrenomedullary AT(1) and AT(2) 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 AT(1) and AT(2) receptor types.
    Annals of the New York Academy of Sciences 07/2004; 1018(1):302-9. DOI:10.1196/annals.1296.036 · 4.38 Impact Factor
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    ABSTRACT: A 2-week pretreatment with an Angiotensin II AT(1) antagonist prevented the adrenomedullary and hormonal response to isolation stress. We studied the effect of life-long treatment with the AT(1) receptor antagonist candesartan, 10 mg/kg/day, or vehicle administered orally in the drinking water from 8 weeks of age on the response to stress of stress-sensitive spontaneously hypertensive rats (SHRs) and their normotensive controls, the Wistar Kyoto (WKY). Rats were submitted to 24-h isolation stress at different times during the treatment. Treatment with candesartan extended the lifespan of SHRs. AT(1) receptor blockade retained its capacity to blunt the response to isolation stress over a long period of treatment. The AT(1) antagonist inhibited epinephrine release in SHR but not in WKY rats during the first 3 months, corticosterone release in SHR and WKY rats during 10 months, and vasopressin release in SHR rats during 18 months of treatment when rats were submitted to isolation stress. There were no changes in vasopressin release in WKY rats during stress or after AT(1) receptor blockade. We conclude that the blockade of the stress response by the AT(1) receptor antagonist is long lasting and differs between stress-prone SHR and WKY rats and that the specific components of the stress response (sympathoadrenal activity, hypothalamic-pituitary-adrenal axis activation, and vasopressin release) react differently to AT(1) receptor blockade. The long-term protective effects of AT(1) receptor blockade can be important in animals vulnerable to stress and, in conjunction with the normalization of blood pressure, can prolong lifespan through end-organ protection.
    Annals of the New York Academy of Sciences 07/2004; 1018(1):131-6. DOI:10.1196/annals.1296.015 · 4.38 Impact Factor
  • C Bregonzio · I Armando · H Ando · M Jezova · G Baiardi · J M Saavedra ·
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    ABSTRACT: 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 AT(1) receptor antagonist candesartan before cold-restraint stress. AT(1) 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 alpha (TNF-alpha) and adhesion protein ICAM-1 in arterial endothelium, and neutrophil infiltration in the gastric mucosa; and decreased PGE(2) content. AT(1) receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, anti-inflammatory effects with reduction in TNF-alpha, and ICAM-1 expression, leading to reduced neutrophil infiltration while maintaining the protective glucocorticoid effects and PGE(2) release. Ang II has a crucial role, through stimulation of AT(1) receptors, in the production and progression of stress-induced gastric injury, and AT(1) receptor antagonists could be of therapeutic benefit.
    Annals of the New York Academy of Sciences 07/2004; 1018(1):351-5. DOI:10.1196/annals.1296.044 · 4.38 Impact Factor
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    ABSTRACT: We isolated a cDNA clone encoding the gerbil AT2 receptor (gAT2) gene from a gerbil adrenal gland cDNA library. The full-length cDNA contains a 1,089-bp open reading frame encoding 363 amino acid residues with 90.9, 96.1, and 95.6% identity with the human (hAT2), rat (rAT2), and mouse AT2 (mAT2) receptors, respectively. There are at least seven nonconserved amino acids in the NH2-terminal domain and in positions Val196, Val217, and Met293, important for angiotensin (ANG) II but not for CGP-42112 binding. Displacement studies in adrenal sections revealed that affinity of the gAT2 receptor was 10-20 times lower for ANG II, ANG III, and PD-123319 than was affinity of the rAT2 receptor. The affinity of each receptor remained the same for CGP-42112. When transfected into COS-7 cells, the gAT2 receptor shows affinity for ANG II that is three times lower than that shown by the hAT2 receptor, whereas affinities for ANG III and the AT2 receptor ligands CGP-42112 and PD-123319 were similar. Autoradiography in sections of the gerbil head showed higher binding in muscles, retina, skin, and molars at embryonic day 19 than at 1 wk of age. In situ hybridization and emulsion autoradiography revealed that at embryonic day 19 the gAT2 receptor mRNA was highly localized to the base of the dental papilla of maxillary and mandibular molars. Our results suggest selective growth-related functions in late gestation and early postnatal periods for the gAT2 receptor and provide an essential basis for future mutagenesis studies to further define structural requirements for agonist binding.
    AJP Regulatory Integrative and Comparative Physiology 01/2004; 285(6):R1373-83. DOI:10.1152/ajpregu.00008.2003 · 3.11 Impact Factor
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    ABSTRACT: Stress reduces gastric blood flow and produces acute gastric mucosal lesions. We studied the role of angiotensin II in gastric blood flow and gastric ulceration during stress. Spontaneously hypertensive rats were pretreated for 14 days with the AT1 receptor antagonist candesartan before cold-restraint stress. AT1 receptors were localized in the endothelium of arteries in the gastric mucosa and in all gastric layers. AT1 blockade increased gastric blood flow by 40-50%, prevented gastric ulcer formation by 70-80% after cold-restraint stress, reduced the increase in adrenomedullary epinephrine and tyrosine hydroxylase mRNA without preventing the stress-induced increase in adrenal corticosterone, decreased the stress-induced expression of TNF-alpha and that of the adhesion protein ICAM-1 in arterial endothelium, decreased the neutrophil infiltration in the gastric mucosa, and decreased the gastric content of PGE2. AT1 receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, and anti-inflammatory effects (with reduction in TNF-alpha and ICAM-1 expression leading to reduced neutrophil infiltration) while maintaining the protective glucocorticoid effects and PGE2 release. Angiotensin 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.
    AJP Gastrointestinal and Liver Physiology 09/2003; 285(2):G414-23. DOI:10.1152/ajpgi.00058.2003 · 3.80 Impact Factor

Publication Stats

411 Citations
53.59 Total Impact Points


  • 2014
    • Catholic University of Córdoba
      Córdoba, Córdoba, Argentina
  • 2010-2014
    • Universidad Católica de Córdoba
      • Facultad de Ciencias Químicas
      Córdoba, Córdoba, Argentina
  • 2007
    • National University of Cuyo
      • Facultad de Ciencias Médicas
      Мендоса, Mendoza, Argentina
    • National University of Cordoba, Argentina
      • Cátedra de Bacteriología y Virología Médicas
      Córdoba, Cordoba, Argentina
  • 2003-2005
    • National Institute of Mental Health (NIMH)
      • Section on Pharmacology
      베서스다, Maryland, United States