Angiotensin-(1-7) is a modulator of the human renin-angiotensin system

Hypertension. 1999 Aug;34(2):296-301. doi: 10.1161/01.hyp.34.2.296.

Abstract

The renin-angiotensin system is important for cardiovascular homeostasis. Currently, therapies for different cardiovascular diseases are based on inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockade. Inhibition of ACE blocks metabolism of angiotensin-(1-7) to angiotensin-(1-5) and can lead to elevation of angiotensin-(1-7) levels in plasma and tissue. In animal models, angiotensin-(1-7) itself causes or enhances vasodilation and inhibits vascular contractions to angiotensin II. The function of angiotensin-(1-5) is unknown. We investigated whether angiotensin-(1-7) and angiotensin-(1-5) inhibit ACE or antagonize angiotensin-induced vasoconstrictions in humans. ACE activity in plasma and atrial tissue was inhibited by angiotensin-(1-7) up to 100%, with an IC(50) of 3.0 and 4.0 micromol/L, respectively. In human internal mammary arteries, contractions induced by angiotensin I and II and the non-ACE-specific substrate [Pro(11),D-Ala(12)]-angiotensin I were antagonized by angiotensin-(1-7) (10(-5) mol/L) in a noncompetitive way, with a 60% inhibition of the maximal response to angiotensin II. Contractions to ACE-specific substrate [Pro(10)]-angiotensin I were also inhibited, an effect only partly accounted for by antagonism of angiotensin II. Angiotensin-(1-5) inhibited plasma ACE activity with a potency equal to that of angiotensin I but had no effect on arterial contractions. In conclusion, angiotensin-(1-7) blocks angiotensin II-induced vasoconstriction and inhibits ACE in human cardiovascular tissues. Angiotensin-(1-5) only inhibits ACE. These results show that angiotensin-(1-7) may be an important modulator of the human renin-angiotensin system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensin I / pharmacology
  • Angiotensin I / physiology
  • Angiotensin II / metabolism
  • Angiotensin II / pharmacology
  • Angiotensin II / physiology*
  • Data Interpretation, Statistical
  • Female
  • Heart Atria / drug effects
  • Heart Atria / metabolism
  • Humans
  • In Vitro Techniques
  • Male
  • Mammary Arteries / drug effects
  • Middle Aged
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / drug effects
  • Peptidyl-Dipeptidase A / metabolism
  • Renin-Angiotensin System / physiology*
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology

Substances

  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • angiotensin I (1-7)