Microglia and brain angiotensin type 1 receptors are involved in desensitising baroreflex by intracerebroventricular hypertonic saline in male Sprague-Dawley rats

High salt diet alters cardiovascular control by increasing concentration of sodium ions (Na+) in cerebrospinal fluid (CSF) and is a risk factor for hypertension. Hypernatremic conditions activate microglia and upregulate renin-angiotensin system in the brain. Thus, we checked if chronic elevation of...

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Veröffentlicht in:Autonomic neuroscience 2019-03, Vol.217, p.49-57
Hauptverfasser: Żera, Tymoteusz, Nowiński, Artur, Segiet, Agnieszka, Smykiewicz, Paweł
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Nowiński, Artur
Segiet, Agnieszka
Smykiewicz, Paweł
description High salt diet alters cardiovascular control by increasing concentration of sodium ions (Na+) in cerebrospinal fluid (CSF) and is a risk factor for hypertension. Hypernatremic conditions activate microglia and upregulate renin-angiotensin system in the brain. Thus, we checked if chronic elevation of CSF Na+ affects neural control of circulatory system via microglia and brain angiotensin type 1 receptors (AT1Rs). Normotensive adult male Sprague-Dawley rats received two-week intracerebroventricular (ICV) infusion of either isoosmotic saline (0.9% NaCl); hyperosmotic saline (5% NaCl); 5% NaCl with minocycline – inhibitor of microglia; 5% NaCl with losartan – AT1R blocker. Fluid intake, urine output, and urinary Na+ excretion were measured before and during ICV infusions. At the end of ICV infusions, blood pressure and heart rate were recorded in awake rats at rest, in response to acute air jet stressor, during pharmacological evaluation of baroreflex, and after autonomic ganglia blockade. CSF and blood were collected for evaluation of Na+ concentration. Baroreflex was blunted in rats ICV infused with 5% NaCl. ICV treatment with losartan or minocycline prevented decrease in baroreflex sensitivity. Hemodynamic parameters at rest, in response to acute stressor and autonomic ganglia blockade were similar in all groups. Neither treatment affected water intake, urine output and urinary Na+ excretion. ICV infusion of 5% NaCl resulted in higher concentration of Na+ in CSF than in control group (0.9% NaCl) and in plasma. Our results indicate that chronic ICV infusion of hyperosmotic saline blunts baroreflex in normotensive rats and this desensitization is mediated by microglia and AT1Rs. •Chronic intracerebroventricular (ICV) infusion of hypertonic saline blunts baroreflex•Treatment with ICV minocycline (microglial inhibitor) prevented baroreflex dysfunction.•Treatment with ICV losartan, AT1R antagonist, prevented baroreflex dysfunction.•Microglia and AT1Rs mediate inhibitory effect of central salt loading on baroreflex.
doi_str_mv 10.1016/j.autneu.2019.01.002
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Hypernatremic conditions activate microglia and upregulate renin-angiotensin system in the brain. Thus, we checked if chronic elevation of CSF Na+ affects neural control of circulatory system via microglia and brain angiotensin type 1 receptors (AT1Rs). Normotensive adult male Sprague-Dawley rats received two-week intracerebroventricular (ICV) infusion of either isoosmotic saline (0.9% NaCl); hyperosmotic saline (5% NaCl); 5% NaCl with minocycline – inhibitor of microglia; 5% NaCl with losartan – AT1R blocker. Fluid intake, urine output, and urinary Na+ excretion were measured before and during ICV infusions. At the end of ICV infusions, blood pressure and heart rate were recorded in awake rats at rest, in response to acute air jet stressor, during pharmacological evaluation of baroreflex, and after autonomic ganglia blockade. CSF and blood were collected for evaluation of Na+ concentration. Baroreflex was blunted in rats ICV infused with 5% NaCl. ICV treatment with losartan or minocycline prevented decrease in baroreflex sensitivity. Hemodynamic parameters at rest, in response to acute stressor and autonomic ganglia blockade were similar in all groups. Neither treatment affected water intake, urine output and urinary Na+ excretion. ICV infusion of 5% NaCl resulted in higher concentration of Na+ in CSF than in control group (0.9% NaCl) and in plasma. 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ICV treatment with losartan or minocycline prevented decrease in baroreflex sensitivity. Hemodynamic parameters at rest, in response to acute stressor and autonomic ganglia blockade were similar in all groups. Neither treatment affected water intake, urine output and urinary Na+ excretion. ICV infusion of 5% NaCl resulted in higher concentration of Na+ in CSF than in control group (0.9% NaCl) and in plasma. Our results indicate that chronic ICV infusion of hyperosmotic saline blunts baroreflex in normotensive rats and this desensitization is mediated by microglia and AT1Rs. •Chronic intracerebroventricular (ICV) infusion of hypertonic saline blunts baroreflex•Treatment with ICV minocycline (microglial inhibitor) prevented baroreflex dysfunction.•Treatment with ICV losartan, AT1R antagonist, prevented baroreflex dysfunction.•Microglia and AT1Rs mediate inhibitory effect of central salt loading on baroreflex.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30704975</pmid><doi>10.1016/j.autneu.2019.01.002</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3535-715X</orcidid></addata></record>
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source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects Air jet stress
Angiotensin II Type 1 Receptor Blockers - pharmacology
Angiotensin type 1 receptor (AT1R)
Animals
Baroreflex
Baroreflex - drug effects
Baroreflex - physiology
Blood pressure
Central nervous system
Infusions, Intraventricular
Losartan
Male
Microglia
Microglia - drug effects
Microglia - physiology
Minocycline
Minocycline - pharmacology
Proinflammatory cytokines
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1 - physiology
Saline Solution, Hypertonic - administration & dosage
Saline Solution, Hypertonic - pharmacology
Sodium
title Microglia and brain angiotensin type 1 receptors are involved in desensitising baroreflex by intracerebroventricular hypertonic saline in male Sprague-Dawley rats
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