Tachycardia evoked from insular stroke in rats is dependent on glutamatergic neurotransmission in the dorsomedial hypothalamus

Fernanda Ribeiro Marins, Marcelo Limborço-Filho, Jennifer A. Iddings, Carlos Henrique Xavier, Vinicia C. Biancardi, Javier E. Stern, Juan Ramiro Diaz, Stephen M. Oppenheimer, Jessica A. Filosa, Marco Antônio Peliky Fontes

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background and purpose: Damage to the insula results in cardiovascular complications. In rats, activation of N-methyl-d-aspartate receptors (NMDARs) in the intermediate region of the posterior insular cortex (iIC) results in sympathoexcitation, tachycardia and arterial pressure increases. Similarly, focal experimental hemorrhage at the iIC results in a marked sympathetic-mediated increase in baseline heart rate. The dorsomedial hypothalamic region (DMH) is critical for the integration of sympathetic-mediated tachycardic responses. Here, whether responses evoked from the iIC are dependent on a synaptic relay in the DMH was evaluated. Methods: Wistar rats were prepared for injections into the iIC and DMH. Anatomical (tracing combined with immunofluorescence) and functional experiments (cardiovascular and sympathetic recordings) were performed. Results: The iIC sends dense projections to the DMH. Approximately 50% of iIC neurons projecting to the DMH express NMDARs, NR1 subunit. Blockade of glutamatergic receptors in the DMH abolishes the cardiovascular and autonomic responses evoked by the activation of NMDARs in the iIC (change in mean arterial pressure 7 ± 1 vs. 1 ± 1 mmHg after DMH blockade; change in heart rate 28 ± 3 vs. 0 ± 3 bpm after DMH blockade; change in renal sympathetic nerve activity 23% ± 1% vs. −1% ± 4% after DMH blockade). Experimental hemorrhage at the iIC resulted in a marked tachycardia (change 89 ± 14 bpm) that was attenuated by 65% ± 5% (p = 0.0009) after glutamatergic blockade at the DMH. Conclusions: The iIC-induced tachycardia is largely dependent upon a glutamatergic relay in the DMH. Our study reveals the presence of an excitatory glutamatergic pathway from the iIC to the DMH that may be involved in the cardiovascular alterations observed after insular stroke.

Original languageEnglish (US)
Pages (from-to)3640-3649
Number of pages10
JournalEuropean Journal of Neurology
Volume28
Issue number11
DOIs
StatePublished - Nov 2021

Keywords

  • autonomic
  • cardiovascular
  • dorsomedial hypothalamus
  • insula
  • rats
  • stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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