Decreased cardiac Ang-(1-7) is associated with salt-induced cardiac remodeling and dysfunction

Ther Adv Cardiovasc Dis. 2010 Feb;4(1):17-25. doi: 10.1177/1753944709353337. Epub 2009 Nov 27.

Abstract

Objective: Angiotensin II has a critical role in the regulation of blood pressure and cell growth and excess activity of the peptide is implicated in the pathogenesis of salt-induced cardiovascular injury. On the other hand, the role of counteracting angiotensin-(1-7) in cardiac structural and functional responses to high salt diet has not been elucidated. Therefore, the present study examined the changes in cardiac angiotensin-(1-7), its forming enzyme angiotensin converting enzyme 2 (ACE2) and receptor mas in response to a high salt diet in spontaneously hypertensive rats (SHR).

Methods: Eight-week-old male spontaneously hypertensive rats (SHR) were given an 8% salt diet for 5 weeks (n = 8). Age- and gender-matched controls received standard chow (n = 6).

Results: Salt excess increased arterial pressure (p < 0.05) and plasma renin and angiotensin II concentrations (p < 0.05). Salt-induced left ventricular remodeling and diastolic dysfunction were associated with diminished levels of angiotensin-(1-7) in the heart (p < 0.05) and no changes in cardiac angiotensin II levels. Exposure to high salt intake decreased cardiac ACE2 mRNA and protein level (p < 0.05). There was no difference in the protein levels of angiotensin II type 1 and mas receptors between the two experimental groups.

Conclusion: The adverse cardiac effects of excessive salt intake may result not only from the undesirable action of angiotensin II but may also be a consequence of diminished protective effects of the angiotensin-(1-7).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / metabolism*
  • Angiotensin II / blood
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Blood Pressure
  • Male
  • Peptide Fragments / metabolism*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred SHR
  • Receptors, G-Protein-Coupled / metabolism
  • Renin / blood
  • Sodium Chloride, Dietary / toxicity*
  • Ventricular Dysfunction, Left / etiology*
  • Ventricular Remodeling*

Substances

  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Sodium Chloride, Dietary
  • Angiotensin II
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2
  • Renin
  • angiotensin I (1-7)