Liliana G Bianciotti | Universidad de Buenos Aires (original) (raw)

Papers by Liliana G Bianciotti

American Journal of Physiology-Heart and Circulatory Physiology

To determine the role of endothelin-1 (ET-1) in the upregulation of atrial natriuretic factor (AN... more To determine the role of endothelin-1 (ET-1) in the upregulation of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) observed in deoxycorticosterone acetate (DOCA)-salt hypertension, the selective ET-1 type-A receptor (ETA) antagonist ABT-627 was chronically administered to normal controls and hypertensive rats. Chronic ETA blockade in DOCA-salt-treated rats prevented the increase in blood pressure and circulating natriuretic protein (NP) levels and partially prevented left ventricular hypertrophy. The changes observed in NP gene expression in the atria were not affected by ABT-627. In the ventricles, ABT-627 reduced NP gene expression. Rats receiving the ETA antagonist alone showed reduced left ventricular NP gene expression. ABT-627 did not affect ventricular collagen III gene expression but enhanced left ventricular α-myosin heavy chain expression. These findings suggest that in vivo, ventricular but not atrial NP production is regulated by ET-1. This differenc...

Pflügers Archiv - European Journal of Physiology

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International journal of molecular sciences, Jan 27, 2018

Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the ... more Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB) also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ET) blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ETblockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented...

The Faseb Journal, Apr 1, 2009

Experimental physiology, Jan 25, 2015

Brain catecholamines participate in diverse biological functions regulated by the hypothalamus. W... more Brain catecholamines participate in diverse biological functions regulated by the hypothalamus. We have previously reported that endothelin-1 and -3 (ET-1 and ET-3) modulate catecholaminergic activity in the anterior and posterior hypothalamus of normotensive rats. The aim of the present study was to evaluate the interaction between ETs and noradrenergic transmission in the posterior hypothalamus of deoxycorticosterone acetate (DOCA)-Salt hypertensive rats. We assessed the effects of ET-1 and ET-3 on tyrosine hydroxylase activity and expression, neuronal noradrenaline (NA) release, neuronal NA transporter (NAT) activity and expression, monoamine oxidase activity, and NA endogenous content and utilization (as a marker of turn-over) in the posterior hypothalamus of DOCA-Salt hypertensive rats. In addition, levels of ETA and ETB receptors were also assayed in normotensive and hypertensive rats. Results showed that TH activity and total and phosphorylated levels, NAT activity and conten...

Molecular medicine (Cambridge, Mass.), Jan 6, 2015

We previously reported that atrial natriuretic factor (ANF) stimulates secretin-evoked cAMP efflu... more We previously reported that atrial natriuretic factor (ANF) stimulates secretin-evoked cAMP efflux through multidrug resistance-associated protein 4 (MRP4) in the exocrine pancreas. Here we sought to establish in vivo whether this mechanism was involved in acute pancreatitis onset in the rat. Rats pretreated with or without probenecid (MRPs general inhibitor) were infused with secretin alone or with ANF. A set of these animals were given repetitive caerulein injections to induce acute pancreatitis. Plasma amylase and intrapancreatic trypsin activities were measured and histological examination of the pancreas performed. Secretin alone activated trypsinogen but induced no pancreatic histological changes. Blockade by probenecid in secretin-treated rats increased trypsin and also induced vacuolization, a hallmark of acute pancreatitis. ANF prevented the secretin response but in the absence of probenecid. In rats with acute pancreatitis, pre-treatment with secretin aggravated the diseas...

American journal of physiology. Gastrointestinal and liver physiology, 2003

Increasing evidence supports the role of atrial natriuretic factor (ANF) in the modulation of gas... more Increasing evidence supports the role of atrial natriuretic factor (ANF) in the modulation of gastrointestinal physiology. The effect of ANF on exocrine pancreatic secretion and the possible receptors and pathways involved were studied in vivo. Anesthetized rats were prepared with pancreatic duct cannulation, pyloric ligation, and bile diversion into the duodenum. ANF dose-dependently increased pancreatic secretion of fluid and proteins and enhanced secretin and CCK-evoked response. ANF decreased chloride secretion and increased the pH of the pancreatic juice. Neither cholinergic nor adrenergic blockade affected ANF-stimulated pancreatic secretion. Furthermore, ANF response was not mediated by the release of nitric oxide. ANF-evoked protein secretion was not inhibited by truncal vagotomy, atropine, or Nomega-nitro-l-arginine methyl ester administration. The selective natriuretic peptide receptor-C (NPR-C) receptor agonist cANP-(4-23) mimicked ANF response in a dose-dependent fashion...

Cellular and molecular neurobiology, 2002

1. We have previously reported that atrial natriuretic factor (ANF) decreases neuronal norepineph... more 1. We have previously reported that atrial natriuretic factor (ANF) decreases neuronal norepinephrine (NE) release. The mechanism that mediates NE release from presynaptic membrane to synaptic cleft is a strongly calcium-dependent process. The modulator effect of ANF may be related to modifications in calcium influx at the presynaptic nerve ending by interaction with voltage-operated calcium channels (VOCCs). 2. On this basis we investigated the effects of ANF on K+-induced 45Ca2+ uptake and evoked neuronal NE release in the presence of specific L-, N-, and P/Q-type calcium channel blockers in the rat hypothalamus. 3. Results showed that ANF inhibited K+-induced 45Ca2+ uptake in a concentration-dependent fashion. Concentration-response curves to VOCC blockers nifedipine (NFD, L-type channel blocker), omega-conotoxin GVIA (CTX, N-type channel blocker), and omega-agatoxin IVA (AGA, P/Q-type channel blocker) showed that all the blockers decreased NE release. Incubation of ANF plus NFD ...

American journal of physiology. Heart and circulatory physiology, 2002

We investigated the effect of long-term in vivo blockade of the ET-1 receptor subtype B (ET(B)) w... more We investigated the effect of long-term in vivo blockade of the ET-1 receptor subtype B (ET(B)) with A-192621, a selective ET(B) antagonist, on atrial and ventricular natriuretic peptide (NP) gene expression in deoxycorticosterone acetate (DOCA)-salt hypertension. In this model, stimulation of the cardiac natriuretic peptide (NP) and the endothelin system and suppression of the renin-angiotensin system is observed. DOCA-salt induced significant hypertension, cardiac hypertrophy and increased NP plasma and left atrial and right and left ventricular NP gene expression. ET(B) blockade per se produced hypertension and left ventricular hypertrophy but induced little change on the levels of ventricular NP and only increased left atrial natriuretic factor (ANF) mRNA levels. Combined ET(B) blockade/DOCA-salt treatment worsened hypertension, increased left ventricular hypertrophy and induced right ventricular hypertrophy. All animals so treated had increased ventricular NP gene expression. C...

Archives internationales de pharmacodynamie et de thérapie

The effects of different concentrations of atrial natriuretic peptide and angiotensin II on [3H]-... more The effects of different concentrations of atrial natriuretic peptide and angiotensin II on [3H]-noradrenaline uptake in hypothalamus and medulla oblongata slices incubated in vitro were determined. Atrial natriuretic peptide, in a dose of 100 mM, increased [3H]-noradrenaline uptake in both regions, while 1 microM of angiotensin II had the opposite effect. The ineffective concentration of 1 nM atrial natriuretic peptide reversed the action of 1 microM of angiotensin II on [3H]-noradrenaline uptake, whereas ineffective concentrations of angiotensin II failed to modify atrial natriuretic peptide effects. These results are compatible with the existence of an atrial natriuretic peptide-angiotensin II interaction in the central nervous system and with the hypothesis that some of the hypotensive effects of atrial natriuretic peptide could occur through modulation of an angiotensin-noradrenergic mechanism in the central nervous system.

Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology, 1991

1. Ten micromoles angiotensin III decreased total 3H-norepinephrine uptake in medulla oblongata o... more 1. Ten micromoles angiotensin III decreased total 3H-norepinephrine uptake in medulla oblongata of the rat and 100 nM atrial natriuretic peptide increased it. These were the threshold concentrations for the peptides to modify the uptake of the amine. 2. A threshold concentrations (1 nM) of atrial natriuretic peptide reversed the effects produced by 10 microM angiotensin III on total 3H-norepinephrine uptake, but subthreshold angiotensin III concentrations failed to alter the effects produced by 100 nM atrial natriuretic peptide. 3. Angiotensin III, as well as atrial natriuretic peptide, modified only neuronal norepinephrine uptake and did not alter non-neuronal norepinephrine uptake. 4. Angiotensin III and atrial natriuretic peptide did not modify the intracellular distribution of norepinephrine in medulla oblongata.

Revista española de fisiología, 1992

The effects of atrial natriuretic peptide (ANP), angiotensin II (ANG II) and angiotensin III (ANG... more The effects of atrial natriuretic peptide (ANP), angiotensin II (ANG II) and angiotensin III (ANG III) on norepinephrine (NE) uptake were studied in the adrenal medulla of the rat. One microM ANG II and 10 microM ANG III decreased NE uptake while 10 nM and 100 nM ANP increased it. Subthreshold concentrations of ANP (1 nM) blunted the inhibitory effect of 1 microM ANG II but did not modify the inhibitory effect of 10 microM ANG III. The increasing effects of 100 nM ANP on NE uptake were partially reversed by subthreshold concentrations of ANG II (1 nM) and blunted by 1 nM ANG III. The interaction between ANP and the renin-angiotensin system could contribute to modulate the sympathetic function in the adrenal medulla.

American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2002

The existence of endothelin binding sites on the catecholaminergic neurons of the hypothalamus su... more The existence of endothelin binding sites on the catecholaminergic neurons of the hypothalamus suggests that endothelins (ETs) participate in the regulation of noradrenergic transmission modulating various hypothalamic-controlled processes such as blood pressure, cardiovascular activity, etc. The effects of ET-1 and ET-3 on the neuronal release of norepinephrine (NE) as well as the receptors and intracellular pathway involved were studied in the rat anterior hypothalamus. ET-1 (10 nM) and ET-3 (10 nM) diminished neuronal NE release and the effect blocked by the selective ET type B receptor antagonist BQ-788 (100 nM). N ω-nitro-l-arginine methyl ester (10 μM), methylene blue (10 μM), and KT5823 (2 μM), inhibitors of nitric oxide synthase activity, guanylate cyclase, and protein kinase G, respectively, prevented the inhibitory effects of both ETs on neuronal NE release. In addition, both ETs increased nitric oxide synthase activity. Furthermore, 100 μM picrotoxin, a GABAA-receptor ant...

Vitamins & Hormones, 2015

Neuronal norepinephrine (NE) uptake is a crucial step in noradrenergic neurotransmission that reg... more Neuronal norepinephrine (NE) uptake is a crucial step in noradrenergic neurotransmission that regulates NE concentration in the synaptic cleft. It is a key mechanism mediated by the NE transporter (NET) which takes the neurotransmitter into the presynaptic neuron terminal or the adrenal medulla chromaffin cell. The activity of NET is short and long terms modulated by phosphorylation mediated by protein kinases A, C, and G and calcium-calmodulin-dependent protein kinase, whereas the transporter availability at the cell surface is regulated by glycosylation. Several neuropeptides like angiotensins II, III, and 1-7, bradykinin, natriuretic peptides, as well as endothelins (ETs) regulate a wide variety of biological effects, including noradrenergic transmission and in particular neuronal NE uptake. Diverse reports, including studies from our laboratory, show that ETs differentially modulate the activity and expression of NET not only in normal conditions but also in diverse cardiovascular diseases such as congestive heart failure and hypertension. Current literature supports a key role for the interaction between ETs and NE in maintaining neurotransmission homeostasis and further suggests that this interaction may represent a potential therapeutic target for various diseases, particularly hypertension.

Regulatory Peptides, 2000

Atrial natriuretic factor (ANF) and C-type natriuretic peptide (CNP) receptors have been describe... more Atrial natriuretic factor (ANF) and C-type natriuretic peptide (CNP) receptors have been described in encephalic areas and nuclei related to the regulation of cardiovascular as well as sodium and water homeostasis. Stimulation of the anterior ventral third ventricular region of the brain modifies plasma ANF concentration, suggesting the participation of the central nervous system in the regulation of circulating ANF. The aim of this work was to study the effect of centrally applied ANF or CNP on plasma ANF. Normal and blood volume expanded rats (0.8 ml isotonic saline / 100 g body weight) were intra cerebralventricularly injected with 1, 10 or 100 ng / ml / min ANF. Blood volume expanded animals were also centrally injected with the same doses of CNP. Blood samples were collected at 5 and 15 min. after intracerebralventricular administration of either ANF or CNP. Centrally applied ANF did not affect circulating ANF in normal blood volume rats. In blood volume expanded animals both ANF (1, 10 or 100 ng / ml / min) and CNP (1 ng / ml / min) decreased plasma ANF concentration after 15 min. Moreover, CNP (10 and 100 ng / ml / min) lowered circulating ANF levels not only at 15 min but also at 5 min. Neither ANF nor CNP elicited any change in mean arterial pressure and heart rate in normal and blood volume expanded rats. These results suggest the existence of a central regulation exerted by natriuretic peptides on circulating ANF levels. Furthermore, this is the first study reporting an effect on plasma ANF induced by centrally applied CNP.

The Open Nutrition Journal, 2008

We have studied hypothalamic noradrenergic activity in relation with bone status in a nutritional... more We have studied hypothalamic noradrenergic activity in relation with bone status in a nutritional growth retardation model (ND). Control rats (C) were fed ad libitum. ND received 80% of the diet consumed by C for 4 weeks and later refed ad libitum for 8 weeks. Food restriction induced detrimental effects on body and femur weight and length (P<0.05) and bone biomechanical properties (P<0.001). Thickness of proliferative and hypertrophic zone (m) of growth plate cartilage and bone volume (%, mean±SE) were 225.96±5.70 v. 280.70±12.52, 95.16±5.81 v. 134.60±9.30, 17.64±3.23 v. 26.80±2.03, respectively (P<0.05); anterior and posterior hypothalamus norepinephrine uptake and release and tyrosine hydroxylase activity (% of control) were 79.05±3.56, 67.00±10.00, 164.26±16.58 and 80.65±5.92, 147.00±1.00, 152.42±9.30, respectively (P<0.05). Thus, impaired biomechanical bone performance in ND could be due, in part, to the increased hypothalamic noradrenergic activity in response to restriction. Normalization of parameters with refeeding suggests no long-term side-effects in undernourished rats.

Regulatory Peptides, 2008

We previously reported that intravenously administered atrial natriuretic factor (ANF) induced no... more We previously reported that intravenously administered atrial natriuretic factor (ANF) induced no salivation but enhanced agonist-evoked secretion in submandibular glands. The gene expression of ANF and natriuretic peptide receptors (NPR) was later reported in the glands. In the present study we sought to establish the intracellular signalling mechanisms underlying ANF modulation of salivary secretion. Fasted rats were prepared with submandibular duct and femoral cannulation. Dose-response curves to methacholine (MC) and norepinephrine (NE) were performed in the presence of cANP (4-23 amide) (selective NPR-C agonist) and ANF. Local injection of the agonist or ANF-induced no salivation, but enhanced MC and NE-evoked secretion. ANF and cANP (4-23 amide) enhanced phosphoinositide turnover being the effect abolished by U73122 (PLC inhibitor). Further ANF and cANP (4-23 amide) decreased basal cAMP content but failed to affect isoproterenol or forskolin-evoked cAMP. ANF response was inhibited by pertussis toxin and mimicked by cANP (4-23 amide) strongly supporting NPR-C activation. ANF-induced cAMP reduction was abolished by PLC and PKC inhibitors. The content of cGMP was dose dependently stimulated by ANF but not modified by cANP (4-23 amide). These findings support that ANF through NPR-C receptors coupled to PLC activation and adenylyl cyclase inhibition interacts with sialogogic agonists in the submandibular gland to potentiate salivation.

Regulatory Peptides, 2004

Based upon the existence of high density of ET-receptors on catecholaminergic neurons of the hypo... more Based upon the existence of high density of ET-receptors on catecholaminergic neurons of the hypothalamus, we studied the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on neuronal norepinephrine (NE) release in the rat posterior hypothalamus. The intracellular pathways and receptors involved were also investigated. Neuronal NE release was enhanced by ET-1 and ET-3 (10 DM). The selective antagonists of subtype A and B ET receptors (ET A , ET B) (100 DM BQ-610 and 100 DM BQ-788, respectively) abolished the increase induced by ET-1 but not by ET-3. The PLC inhibitor, U73122 (10 AM), abolished ET-1 and ET-3 response. GF-109203X (100 DM) (PKC inhibitor) blocked the increase in NE release produced by ET-3 and partially blocked ET-1 response. The inositol 1,4,5-trisphosphate-induced calcium release inhibitor, 42 AM 2-APB, inhibited the stimulatory effect induced by ET-3 but not by ET-1. The PKA inhibitor, 500 DM H-89, blocked the increase in neuronal NE release evoked by ET-1 but not by ET-3. Our results showed that ET-1 as well as ET-3 displayed an excitatory neuromodulatory effect on neuronal NE release in the rat posterior hypothalamus. ET-1 through an atypical ET A or ET B receptor activated the PLC/PKC signalling pathway as well as the cAMP pathway, whereas ET-3 through a nonET A /non-ET B receptor activated the phosphoinositide pathway. Both ETs would enhance the sympathoexcitatory response elicited by the posterior hypothalamus and thus participate in cardiovascular regulation.