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

Abstract

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.

• Authors: May Al-Maghrebi, Ibrahim F Benter, Debra I Diz
• Journal: Pharmacological research (Pharmacol Res) Vol. 59 Issue 4 Pg. 263-8 (Apr 2009) ISSN: 1043-6618 [Print] Netherlands
• PMID: 19166939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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)

Topics

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