Effect of apelin on the cardiac hemodynamics in hypertensive rats with heart failure

Abstract

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.

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

“…At 4 weeks, obvious myocardial fibrosis was observed, which was consistent with the increased markers of fibrosis (collagen high I and collagen high III and fibronectin) [61]. In 3 other studies that used needles and thread of the same specification, the occurrence time of myocardial fibrosis was different at 15 days [62], 6 weeks [63], and 17 weeks [64].…”

Apelin: an antithrombotic factor that inhibits platelet function

“…Of interest, although the stimulatory effect of apelin on cGMP was reported for various cell types, 34,35 apelin was found to induce or inhibit cAMP. 36,37 In the presence of thrombin, platelets increased their cGMP accumulation, which further increased in the presence of apelin ( Figure 3B). Previously, cGMP was reported to have a biphasic response in platelets: an initial, transient effect associated with the activation/aggregation of platelets, and a delayed mechanism associated with platelet inhibition.…”

The Emerging Potential of the Apelin-APJ System in Heart Failure

“…A similar observation has been noted in a mouse model of hypertension-induced HF. 44 Further work is therefore required to confirm and elucidate this mechanism.…”

“…51e53 In a model of progressive LV pressure overload, rats in a pre-HF compensatory LV hypertrophy phase show no difference in myocardial apelin and APJ levels from control animals 54 ; however, progression to overt HF results in significant down-regulation of both myocardial apelin and APJ levels and circulating apelin levels. 16,43,44,51,52,54,55 Treatment with an ARB, 52,54 but not a b-blocker or matrix metalloproteinase inhibitor, 54 restores myocardial apelin and APJ levels. A similar recent study by the same group investigated the effects of a chronic infusion of pyr1-apelin-13 in the same rat hypertensive heart failure model.…”