Interaction of bradykinin and angiotensin-(1-7) in the central modulation of the baroreflex control of the heart rate

J Hypertens. 1998 Dec;16(12 Pt 1):1797-804. doi: 10.1097/00004872-199816120-00013.

Abstract

Objective: Previous studies have shown that angiotensin-(1-7) potentiates the vascular actions of bradykinin. In the present study, we evaluated the interaction of bradykinin and angiotensin-(1-7) in the central modulation of baroreflex control of the heart rate.

Materials and methods: Blood pressure and reflex bradycardia, elicited by intravenous injection of phenylephrine, were evaluated in conscious male Wistar rats before and at the end of 1 h of an intracerebroventricular infusion of angiotensin-(1-7) at 0.5 or 1.0 microg/h combined with bradykinin at 2.5 microg/h; or angiotensin-(1-7) at 2.0 microg/h combined with bradykinin at 4.0 microg/h; or angiotensin-(1-7) alone at 2.0 or 4.0 microg/h; or bradykinin alone at 4.0 or 8.0 microg/h; or saline at 8 microl/h. In addition, baroreflex bradycardia was evaluated before and at the end of 1 and 2 h of intracerebroventricular infusion of angiotensin-(1-7) at 4 microg/h for 2 h; or saline at 8 microl/h in the first hour followed by HOE 140 at 90 ng/h in the second hour; or angiotensin-(1-7) at 4 microg/h in the first hour followed by angiotensin-(1-7) at 4 microg combined with HOE 140 at 90 ng/h in the second hour; or HOE 140 at 90 ng/h in the first hour followed by HOE 140 at 90th ng/h combined with angiotensin-(1-7) at 4 microg/h in the second hour; or saline at 8 microl/h for 2 h.

Results: The intracerebroventricular infusion of angiotensin-(1-7) or bradykinin alone required a dose of 4.0 and 8.0 microg/h, respectively, to facilitate baroreflex control of the heart. However, a simultaneous infusion of these peptides at subeffective rates was able to produce a significant increase in baroreflex sensitivity. In addition, the facilitation of the baroreflex control of the heart rate induced by angiotensin-(1-7) at 4.0 microg/h was inhibited by HOE 140.

Conclusions: These results suggest that centrally, bradykinin and angiotensin-(1-7) can interact in order to modulate baroreflex control of the heart rate. In addition, our data indicate that the central modulatory effect of angiotensin-(1-7) on the baroreflex is mediated, at least in part, by the release of kinins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists
  • Angiotensin I
  • Angiotensin II / administration & dosage
  • Angiotensin II / antagonists & inhibitors
  • Angiotensin II / pharmacology*
  • Animals
  • Baroreflex / drug effects*
  • Baroreflex / physiology
  • Bradykinin / administration & dosage
  • Bradykinin / analogs & derivatives
  • Bradykinin / metabolism
  • Bradykinin / pharmacology*
  • Bradykinin Receptor Antagonists
  • Drug Synergism
  • Heart Rate / drug effects*
  • Heart Rate / physiology
  • Injections, Intraventricular
  • Male
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Adrenergic beta-Antagonists
  • Bradykinin Receptor Antagonists
  • Peptide Fragments
  • Angiotensin II
  • icatibant
  • Angiotensin I
  • angiotensin I (1-7)
  • Bradykinin