# Co-administration of isoprenaline and phenylephrine induced a new HFrEF mouse model through activation of both SNS and RAAS

## TL;DR

A new mouse model of heart failure was created using isoprenaline and phenylephrine, which activates both SNS and RAAS, making it more similar to human heart failure.

## Contribution

A novel heart failure mouse model is introduced that activates both SNS and RAAS pathways, offering a more human-like representation.

## Key findings

- The ISO/PE model activates both SNS and RAAS pathways, unlike ISO alone.
- RNA sequencing showed upregulation of genes related to hypertrophy, fibrosis, SNS, and RAAS.
- The model is more representative of human heart failure due to dual receptor activation.

## Abstract

The pathogenesis of human heart failure is diverse, and a large number of animal models have emerged to better understand the development of heart failure in humans. Among them, there are several methods of induction in mouse heart failure models, each with its advantages and disadvantages. The use of drug induced heart failure models has greatly facilitated basic research and reduced the disadvantages of time-consuming and labor-intensive surgical modeling.

In our experiments, we used a combination of isoprenaline (ISO) and phenylephrine (PE) for modeling; we aimed to evaluate whether it is superior to conventional drug-induced models, especially those induced by isoprenaline alone. The ISO and PE were administered for 2 weeks by subcutaneous implantation with a micro-osmolar pump, and the mice were monitored dynamically for cardiac ultrasound and blood pressure.

RNA sequencing of myocardial tissues after execution of mice further clarified that hypertrophy, fibrosis genes, Sympathetic nervous system (SNS), and Renin-angiotensin-aldosterone system (RAAS) pathways were upregulated.

Therefore, we conclude that the ISO/PE-induced mouse heart failure model can activate both the SNS and RAAS, through the activation of both α-adrenergic receptor (α-AR) and β-adrenergic receptor (β-AR), which is more consistent with the development of human heart failure than the ISO-induced model and is expected to be a unique and representative heart failure modeling method.