Alterations of the renin-angiotensin system at the RVLM of transgenic rats with low brain angiotensinogen

Am J Physiol Regul Integr Comp Physiol. 2001 Feb;280(2):R428-33. doi: 10.1152/ajpregu.2001.280.2.R428.

Abstract

The transgenic rats TGR(ASrAOGEN) (TGR) with low levels of brain angiotensinogen were analyzed for cardiovascular reactivity to microinjections of ANG II and angiotensin receptor (AT(1)) antagonists [CV-11974, AT(1) specific; A-779, ANG-(1--7) selective; sarthran, nonspecific] into the rostral ventrolateral medulla (RVLM) of conscious rats. Microinjection of ANG II resulted in a significantly higher increase in the mean arterial pressure (MAP) of TGR than control [Sprague-Dawley (SD)] rats, suggesting an upregulation of ANG II receptors in TGR. CV-11974 produced an increase in MAP of SD but not in TGR rats. A-779 produced a depressor response in SD but not in TGR rats. Conversely, sarthran produced a similar decrease of MAP in both rat groups. The pressor effect of the AT(1) antagonist may indicate an inhibitory role of AT(1) receptors in the RVLM. On the other hand, ANG-(1--7) appears to have a tonic excitatory role in this region. The altered response to specific angiotensin antagonists in TGR further supports the functionally relevant decrease in angiotensins in the brains of TGR and corroborates the importance of the central renin-angiotensin system in cardiovascular homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / pharmacology
  • Angiotensinogen / deficiency
  • Angiotensinogen / genetics
  • Angiotensinogen / physiology*
  • Animals
  • Animals, Genetically Modified
  • Antihypertensive Agents / pharmacology
  • Benzimidazoles / pharmacology
  • Biphenyl Compounds
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Brain / physiology*
  • Functional Laterality
  • Heart Rate / drug effects
  • Heart Rate / physiology*
  • Male
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / physiology*
  • Microinjections
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System / physiology*
  • Tetrazoles / pharmacology

Substances

  • 7-Ala-angiotensin (1-7)
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Peptide Fragments
  • Tetrazoles
  • Angiotensinogen
  • Angiotensin II
  • angiotensin II, Sar(1)-Thr(8)-
  • candesartan