Ang-(1-7) might prevent the development of monocrotaline induced pulmonary arterial hypertension in rats.

OBJECTIVES

To investigate whether Angiotensin-(1-7) [Ang-(1-7)] could prevent the development of monocrotaline (MCT) induced pulmonary arterial hypertension and vascular remodeling.

MATERIALS AND

METHODS

30 Sprgue-Dawely rats were randomly assigned into three groups: control group, pulmonary arterial hypertension (PAH) group and PAH +Ang-(1-7) group. Rats in PAH group and PAH +Ang-(1-7) group received 60 mg/kg monocrotaline (MCT) injection subcutaneously and after 24 hours received either saline or 24 microg/kg/h of Ang-(1-7) injection via osmotic minipumps for 4 weeks. Those rats in control group were firstly injected saline subcutaneously and then received saline injection via osmotic minipumps.

RESULTS

After four weeks, in PAH group, right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), percentage of wall thickness (WT%) and percentage of wall area (WA%) were significantly increased, and the level of endothelial nitric oxide synthase (eNOS) protein, eNOS ser 1177-phosphorylati, Akt-phosphorylation were significantly decreased compared with control group. However, RVSP, RVHI, WT%, WA% were dramatically decreased in PAH+Ang-(1-7) group and the level of eNOS protein, eNOS ser 1177-phosphorylation, Akt-phosphorylation were significantly increased compared with PAH group.

CONCLUSION

Those results suggest that Ang-(1-7) could prevent the development of monocrotaline induced pulmonary arterial hypertension and vascular remodeling, which appears to be associated with up-regulation of eNOS activation via Akt pathway.