Angiotensin-(2-7): A novel antihypertensive peptide of the renin-angiotensin-system
Abstract Body: Recently, it has been described that acetyl-angiotensin (2-7)-amide (Ac-Ang-(2-7)-NH2) is a potent ACE inhibitor. In addition, the putative endogenous peptide angiotensin-(2-7) was also reported to be an ACE inhibitor. Here we tested the effect of Ang-(2-7) in blood pressure (BP) and isolated aortic rings of Wistar and SHR. In addition, we evaluated whether this hexapeptide stimulates receptors from the alternative renin-angiotensin system (RAS), including Mas, MrgD, and AT2R using CHO-transfected cells. To record BP and administer drugs, the femoral arterial and vein were cannulated. In the baseline period, BP was recorded for 1 hour. In bolus intravenous injection of Ang-(2-7) was performed at doses of 30, 6, and 2.4 μg/kg, in a volume of 0,1 ml/100g. After the injection BP and heart rate (HR) were recorded for six hours. Additionally, we evaluated the effect of Ang-(2-7) in isolated aortic rings from SHR and Wistar rats, pre-constricted with phenylephrine (10-7mol.L-1). The peptide effect was tested in the range of 10-12 to 10-6 molar. The effect of the peptide was also evaluated in endothelium-denuded rings. Furthermore, the effect of Ang-(2-7) was tested in rings pre-treated with the Mas/MrgD antagonist D-Pro7-Ang-(1-7) (10-6 μmol.L-1). Finally, we used NO intracellular measurements to test for the Ang-(2-7) activation of Mas, MrgD, or AT2 receptors using transfected-CHO cells. To confirm the effectiveness of Ang-(2-7) for NO production we used 4,5-diaminofluorescein-diacetate (DAF-FM diacetate) and the human umbilical vein cell line EA.hy926. Our data showed a progressive and marked reduction in BP reaching -40 mmHg (123±12mmHg;n=3) with 6 hours after 30ug/kg administration of injection of Ang-(2-7). There was no significant effect on Blood pressure in Wistar rats after injection. The aortic rings had a vasorelaxing effect of the Ang-(2-7) in both Wistar and SHR, which was abolished after endothelium was removed. The vasorelaxant effect of Ang-(2-7) was abolished by pre-treatment with D-Pro7-Ang-(1-7). Accordingly, Ang-(2-7) induced NO production in EA.hy926 and MrgD-transfected CHO cells. A slight effect on NO production was also observed in AT2-transfected cells. In conclusion, we have identified a new biologically active component of the RAS with a potent antihypertensive effect in SHR. Our results suggest an important contribution of MrgD/NO to the Ang-(2-7) cardiovascular effects.
Barros, Carolina
( UFMG
, Belo Horizonte
, Brazil
)
Nakaie, Clovis
( UNIFESP
, São Paulo
, Brazil
)
Silva, Rogerio
( UNIFESP
, São Paulo
, Brazil
)
Bersanetti, Patricia
( UNIFESP
, São Paulo
, Brazil
)
Carmona, Adriana
( UNIFESP
, São Paulo
, Brazil
)
Leite, M. Fatima
( UFMG
, Belo Horizonte
, Brazil
)
Santos, Robson
( UFMG
, Belo Horizonte
, Brazil
)
Ferraz, Kamylle
( UFMG
, Belo Horizonte
, Brazil
)
Chaves, Sthefanie
( UFMG
, Belo Horizonte
, Brazil
)
Bessa, Amanda
( UFMG
, Belo Horizonte
, Brazil
)
Vieira-machado, Uri
( UFMG
, Belo Horizonte
, Brazil
)
Feng, Isadora
( UFMG
, Belo Horizonte
, Brazil
)
Itaborahy, Matheus
( UFMG
, Belo Horizonte
, Brazil
)
Monteiro, Adelson
( UFMG
, Belo Horizonte
, Brazil
)
Silva, Filipe
( UFMG
, Belo Horizonte
, Brazil
)
Author Disclosures:
Carolina Barros:DO NOT have relevant financial relationships
| Clovis Nakaie:No Answer
| Rogerio Silva:No Answer
| Patricia Bersanetti:No Answer
| Adriana Carmona:No Answer
| M. Fatima Leite:No Answer
| Robson Santos:DO NOT have relevant financial relationships
| Kamylle Ferraz:DO have relevant financial relationships
;
Research Funding (PI or named investigator):CNPq:Active (exists now)
; Research Funding (PI or named investigator):CAPES:Active (exists now)
; Research Funding (PI or named investigator):FAPEMIG:Active (exists now)
| Sthefanie Chaves:No Answer
| Amanda Bessa:No Answer
| Uri Vieira-Machado:No Answer
| Isadora Feng:DO NOT have relevant financial relationships
| Matheus Itaborahy:No Answer
| Adelson Monteiro:No Answer
| Filipe Silva:No Answer
