Tonic neuronal inhibition by AII revealed by iontophoretic application of Losartan, a specific antagonist of AII type-1 receptors

Brain Res Bull. 1994;34(6):533-9. doi: 10.1016/0361-9230(94)90137-6.

Abstract

Short-term low-dose mineralocorticoid pretreatment enhances subsequent neuronal activity in the medial septum/preoptic region and in the stria terminalis/posterior amygdala of urethane anaesthetised male Wistar rats and sensitises these neurons to angiotensin II (AII). We have investigated the effect of iontophoretic application of Losartan, a specific nonpeptidergic AII type-1 receptor antagonist, on the background activity of spontaneously active neurons in these regions using a seven-barrelled microiontophoretic electrode sealed to a recording electrode. The influence of Losartan on the effects of iontophoretically applied AII in deoxycorticosterone acetate (DOCA) pretreated and nonpretreated rats was also investigated. Iontophoretically applied Losartan was observed to block the excitatory effect of AII in some neurons. In other spontaneously active neurons Losartan was seen to stimulate (or inhibit) immediately, this effect being greater in nonpretreated than in DOCA pretreated rats. Losartan was also observed to provoke persistent excitation of some spontaneously active neurons only in the nonpretreated rats. These results suggest that there exists a tonic inhibition by AII on the neurons in this area of the forebrain and that there may exist at least two subtypes of the AII type-1 receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldosterone / pharmacology
  • Amygdala / cytology
  • Amygdala / drug effects
  • Angiotensin II / antagonists & inhibitors
  • Angiotensin II / pharmacology*
  • Angiotensin Receptor Antagonists*
  • Animals
  • Biphenyl Compounds / pharmacology*
  • Desoxycorticosterone / pharmacology
  • Imidazoles / pharmacology*
  • Iontophoresis
  • Losartan
  • Male
  • Neurons / drug effects*
  • Preoptic Area / cytology
  • Preoptic Area / drug effects
  • Prosencephalon / cytology
  • Prosencephalon / drug effects
  • Rats
  • Rats, Wistar
  • Septum Pellucidum / cytology
  • Septum Pellucidum / drug effects
  • Tetrazoles / pharmacology*

Substances

  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Imidazoles
  • Tetrazoles
  • Angiotensin II
  • Desoxycorticosterone
  • Aldosterone
  • Losartan