AT1 receptors mediate excitatory inputs to rostral ventrolateral medulla pressor neurons from hypothalamus

Tatsuya Tagawa, Roger A L Dampney*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)

Abstract

Angiotensin II type I (AT1) receptors are located on pressor neurons in the rostral ventrolateral medulla, and their activation results in an increase in arterial pressure. However, the normal role of these AT1 receptors in cardiovascular regulation is unknown. In this study, we tested the hypothesis that these receptors mediate synaptic excitation of rostral ventrolateral medullary pressor neurons in response to activation of the hypothalamic paraventricular nucleus. In anesthetized rats, microinjections of the γ-aminobutyric acid receptor antagonist bicuculline were made into the paraventricular nucleus; this injection causes activation of the nucleus as a consequence of disinhibition. The pressor and sympathoexcitatory responses evoked by paraventricular nucleus activation were significantly reduced (by ≃40% to 50%) after microinjection of the specific AT1 receptor antagonists losartan or L-158,809 into the rostral ventrolateral medulla on the ipsilateral, but not contralateral, side. These responses were reduced to a similar degree after microinjections of the neuroinhibitory compound muscimol into the ipsilateral, but not contralateral, rostral ventrolateral medulla. However, bilateral microinjections of the glutamate receptor antagonist kynurenic acid into the rostral ventrolateral medulla had no effect on the responses evoked from the paraventricular nucleus. Conversely, bilateral microinjections of kynurenic acid into the rostral ventrolateral medulla virtually abolished the somatosympathoexcitatory reflex, whereas bilateral microinjections of losartan or L-158,809 had no effect on this reflex. The results indicate that excitatory synaptic inputs to pressor neurons in the rostral ventrolateral medulla arising from activation of the paraventricular nucleus are mediated predominantly by AT1 receptors.

Original languageEnglish
Pages (from-to)1301-1307
Number of pages7
JournalHypertension
Volume34
Issue number6
Publication statusPublished - Dec 1999
Externally publishedYes

Keywords

  • Angiotensin II
  • Bicuculline
  • Blood pressure
  • Blood vessels
  • Brain
  • Receptors, glutamate

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