Endogenous angiotensin-(1-7) reduces cardiac ischemia-induced dysfunction in diabetic hypertensive rats

Pharmacol Res. 2009 Apr;59(4):263-8. doi: 10.1016/j.phrs.2008.12.008. Epub 2008 Dec 31.


Angiotensin-(1-7) [Ang-(1-7)] is a vasodilator peptide with cardiac and vascular protective properties. We examined the influence of Ang-(1-7), both endogenous and after chronic treatment with the peptide (576microg/(kgday)), on ischemia/reperfusion (I/R)-induced cardiac dysfunction in streptozotocin-treated spontaneously hypertensive rats (diabetic SHR). In isolated perfused hearts, recovery of left ventricular function from 40min of global ischemia was improved significantly in Ang-(1-7)- or captopril-treated diabetic SHR and worsened in animals treated with A779, an Ang-(1-7) receptor (AT((1-7))) antagonist. The beneficial effect of captopril on cardiac recovery was reduced when co-administered with A779. Cardiac NF-kappaB activity appears to be higher in diabetic SHR and treatment with Ang-(1-7) or captopril decreased NF-kappaB activity in diabetic SHR, an effect partially reversed by co-administration of A779. Real-time PCR-based gene array analysis of cardiac tissue revealed that Ang-(1-7) or captopril treatment may reduce expression of several genes of inflammation involved in the NF-kappaB signalling pathway. The data provide for the first time a role for endogenous Ang-(1-7) as well as confirmation that exogenous treatment with the peptide produces cardioprotection. Whether potential anti-inflammatory and transcriptional factor changes are directly linked to the cardioprotection produced by Ang-(1-7) in diabetic SHR remains to be determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / administration & dosage
  • Angiotensin I / antagonists & inhibitors
  • Angiotensin I / physiology*
  • Angiotensin I / therapeutic use*
  • Angiotensin II / administration & dosage
  • Angiotensin II / analogs & derivatives
  • Angiotensin II / therapeutic use
  • Angiotensin Receptor Antagonists
  • Animals
  • Blood Pressure / drug effects
  • Captopril / administration & dosage
  • Captopril / therapeutic use
  • Diabetes Mellitus, Experimental / physiopathology
  • Drug Therapy, Combination
  • Heart / drug effects*
  • Heart / physiopathology
  • In Vitro Techniques
  • Male
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardium / enzymology
  • NF-kappa B / metabolism
  • Nuclear Proteins / metabolism
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / physiology*
  • Peptide Fragments / therapeutic use*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Angiotensin / agonists
  • Signal Transduction / drug effects


  • 7-Ala-angiotensin (1-7)
  • Angiotensin Receptor Antagonists
  • NF-kappa B
  • Nuclear Proteins
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Angiotensin
  • Angiotensin II
  • Angiotensin I
  • Captopril
  • angiotensin I (1-7)