Activation of hypothalamic angiotensin receptors produces pressor responses via cholinergic inputs to the rostral ventrolateral medulla in normotensive and hypertensive rats

Brain Res. 2002 Oct 25;953(1-2):232-45. doi: 10.1016/s0006-8993(02)03297-3.


We have previously reported that the angiotensin system in the anterior hypothalamic area (AHA) is enhanced in spontaneously hypertensive rats (SHR) and that this enhancement is involved in hypertension in SHR. In addition, acetylcholine (ACh) release is increased in the rostral ventrolateral medulla (RVLM) of SHR, which has also been shown to be involved in hypertension in SHR. In this study, we examined whether the enhanced angiotensin system in the AHA of SHR is related to the increase in cholinergic inputs to the RVLM. Electrical stimulation in the AHA produced a pressor response and an increase in firing rate of RVLM barosensitive neurons. These responses were inhibited and enhanced by RVLM application of the muscarinic receptor antagonist scopolamine and the cholinesterase inhibitor physostigmine, respectively. AHA stimulation also produced release of ACh in the RVLM. Microinjections of angiotensin II and carbachol into the AHA produced pressor responses. The pressor response to angiotensin II was inhibited by scopolamine microinjected into the RVLM, although this produced no effect on the response to carbachol. In SHR, although not in Wistar-Kyoto rats, microinjection of losartan into the AHA inhibited pressor responses to physostigmine. However inhibition was not observed in response to the directly acting muscarinic receptor agonist carbachol, injected into the RVLM. These findings demonstrate that angiotensin receptor activation or electrical stimulation in the AHA produce a pressor response via an increase in ACh release in the RVLM. In addition, the present study suggests that the enhanced angiotensin system in the AHA of SHR increases cholinergic inputs to the RVLM, which leads to increases in blood pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Angiotensin II / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Cholinergic Fibers / physiology
  • Cholinesterase Inhibitors / pharmacology
  • Electric Stimulation
  • Hypertension / physiopathology*
  • Hypothalamus, Anterior / cytology
  • Hypothalamus, Anterior / physiology*
  • Iontophoresis
  • Losartan / pharmacology
  • Male
  • Medulla Oblongata / cytology
  • Medulla Oblongata / physiology*
  • Microinjections
  • Muscarinic Antagonists / pharmacology
  • Neural Pathways
  • Physostigmine / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Angiotensin / metabolism*
  • Scopolamine / pharmacology
  • Vasoconstrictor Agents / pharmacology
  • gamma-Aminobutyric Acid / pharmacology


  • Antihypertensive Agents
  • Cholinergic Agonists
  • Cholinesterase Inhibitors
  • Muscarinic Antagonists
  • Receptors, Angiotensin
  • Vasoconstrictor Agents
  • Angiotensin II
  • gamma-Aminobutyric Acid
  • Carbachol
  • Physostigmine
  • Scopolamine
  • Losartan
  • Acetylcholine