It is known that
apelin has definite protective effects on various
cardiovascular diseases; however, the mechanism through which
hypertension with
heart failure (H-HF) is affected by pyroglutamylated
apelin-13 (Pyr-AP13) remain unclear. Thus, in the present study, we investigated the effects of
apelin on the cardiac hemodynamics in rats with
hypertension and
heart failure. In our study, cardiac function, dimensions and histological determination of the
fibrosis of rats with two-kidney, one-
clip induced
hypertension and
sham-operated rats were assessed using an echocardiography system and Masson's trichrome. The infusion of either 5%
glucose injection (GS) alone or 5% GS containing Pyr-AP13 as a dose, time-matched design on the cardiac hemodynamics in H-HF rats and
sham-operated rats was recorded. For the determination of the effects of potential related
proteins on cardiac hemodynamics in the H-HF rats, the animals were divided into 5 groups: i) the
sham-operated group (n=8); ii) H-HF (n=8); iii) H-HF with infusion of 0.1 µg dose of Pyr-AP13 (n=8) or 5%
glucose (GS) (n=8); iv) H-HF with infusion of 1 µg dose of Pyr-AP13 (n=8) or 5% GS (n=8); and v) H-HF with infusion of 10 µg dose of Pyr-AP13 (n=8) or 5% GS (n=8). The concentration of cyclic
adenosine 3',5'-monophosphate (cAMP) was determined by ELISA. The expression of membrane and cytosolic
proteins was evaluated by western blot analysis. Significant cardiac and perivascular
fibrosis was observed in the H-HF rats. Following the infusion of Pyr-AP13, the systolic and diastolic function was significantly improved in the cardiac hemodynamic parameters in the H-HF rats treated with Pyr-AP13. The
apelin receptor (APJ), which was activated by the exogenous infusion of Pyr-AP13, was partially recycled from the cytoplasm back to the plasma membrane; however, membrane APJ was eventually downregulated in the H-HF rats treated with Pyr-AP13 compared with the
sham-operated group rats. Our findings suggested that a complex was formed after Pyr-AP13 combined with cellular membrane APJ receptor. However, the endogenous downregulation of the APJ receptor results in benefits from the exogenous administration of
apelin.