Angiotensin-(3-7) pressor effect at the rostral ventrolateral medulla

Regul Pept. 2007 Jun 7;141(1-3):168-74. doi: 10.1016/j.regpep.2006.12.031. Epub 2007 Jan 20.

Abstract

Ang-(3-7) is a fragment of the renin-angiotensin system that can be derived both from Ang II or Ang-(1-7). In the present study we determined the cardiovascular effects produced by angiotensin-(3-7) [Ang-(3-7)] microinjection into the rostral ventrolateral medulla (RVLM), a key region for the control of sympathetic drive to the periphery. RVLM microinjection of Ang-(3-7) (20, 40 or 80 ng) in male Wistar rats anesthetized with urethane produced significant increases in MAP (19+/-3.8 mm Hg, n=5; 16+/-1.6 mm Hg, n=15 and 11+/-1.2 mm Hg, n=4, respectively) as compared to saline (4+/-0.7 mm Hg, n=6). These alterations were similar to that induced by Ang-(1-7) (14+/-1.3 mm Hg, 40 ng; n=12) and Ang II (17+/-2.3 mm Hg, 40 ng; n=7). Microinjection of losartan (AT(1) receptor antagonist, 100 pmol) or A779 (selective Mas receptor antagonist, 100 pmol) did not alter the pressor effect caused by Ang-(3-7). Microinjection of an Ang-(3-7) analogue, d-Ala(7)-Ang-(3-7) (100 pmol), completely abolished the pressor effect caused by Ang-(3-7). These results suggest that Ang-(3-7) may be an additional peptide of the RAS to act as neuromodulator, at least at the RVLM. Further, the Ang-(3-7) pressor effect is not mediated by the interaction with AT(1) or the Ang-(1-7), Mas, receptors.

MeSH terms

  • Anesthetics, Intravenous / pharmacology
  • Angiotensin I / administration & dosage
  • Angiotensin I / antagonists & inhibitors
  • Angiotensin I / pharmacology*
  • Angiotensin II / analogs & derivatives
  • Angiotensin II / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects*
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Losartan / pharmacology
  • Male
  • Medulla Oblongata / anatomy & histology*
  • Medulla Oblongata / drug effects*
  • Microinjections
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / pharmacology*
  • Pulsatile Flow / drug effects
  • Rats
  • Rats, Wistar
  • Urethane / pharmacology

Substances

  • 7-Ala-angiotensin (1-7)
  • Anesthetics, Intravenous
  • Antihypertensive Agents
  • Peptide Fragments
  • Angiotensin II
  • Urethane
  • Angiotensin I
  • angiotensin I (1-7)
  • Losartan