Correlation between ACE2 and monocrotaline-induced pulmonary arterial hypertension in rats

The fatality rate of pulmonary arterial hypertension (PAH) is high. This study aimed to determine the correlation between ACE2 and monocrotaline (MCT)-induced PAH in rats.

Rats were randomly divided into 4 groups: control group; MCT group; resorcinolnaphthalein (Rec) group; and Rec + A779 (Mas receptor antagonist) group. Rats in the control group received a single subcutaneous injection of normal saline on the 1^st d, and an osmotic pump capsule combining normal saline subcutaneously since the 2^nd d. The rats in the other 3 groups received a single subcutaneous injection of MCT on the 1^st d. An osmotic minipumps containing normal saline, Rec, and Rec + A779 were implanted in rats in the MCT, Rec, and Rec + A779 groups, respectively.

The PAH rat model was successfully constructed with MCT. ACE2 reduced the mPAP, right ventricular hypertrophy index, and pulmonary artery media in the PAH rats (p < 0.05). Rec activated ACE2 expression and significantly increased the Mas levels, phospho-Akt (P-Akt), and phospho-eNOS (P-eNOS) in lung tissues of PAH rats (p < 0.05). The mPAP, right ventricular hypertrophy index, and pulmonary artery media in the Rec + A779 group were significantly increased compared to the blank and Rec groups (p < 0.05). The Mas level, P-Akt, and P-eNOS in rat lung tissues were significantly decreased in the Rec + A779 group compared to the Rec group (p < 0.05).

Rec upregulates ACE2 expression, and this elevated ACE2 expression may be associated with amelioration of MCT‑induced PAH in rats, likely through the downstream Akt/eNOS signaling pathway.