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

  • Tymoteusz Żera
    Correspondence
    Corresponding author at: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, the Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
    Affiliations
    Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, the Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland
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  • Artur Nowiński
    Affiliations
    Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, the Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland
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  • Agnieszka Segiet
    Affiliations
    Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, the Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland
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  • Paweł Smykiewicz
    Affiliations
    Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, the Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland
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Published:January 06, 2019DOI:https://doi.org/10.1016/j.autneu.2019.01.002

      Highlights

      • 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

      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.

      Keywords

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