Endogenous angiotensin-(1-7) reduces cardiac ischemia-induced dysfunction in diabetic hypertensive rats.
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.
Al-Maghrebi
May
M
Department of Biochemistry, Faculty of Medicine, Kuwait University, Kuwait.
Benter
Ibrahim F
IF
Diz
Debra I
DI
D000803:Angiotensin I / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use*; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004359:Drug Therapy, Combination; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000201:enzymology; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000819:agonists; D015398:Signal Transduction / Q000187:drug effects
C092006:7-Ala-angiotensin (1-7); D057911:Angiotensin Receptor Antagonists; D016328:NF-kappa B; D009687:Nuclear Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; C118790:angiotensin I (1-7)