Comparison of hypoxia-induced pulmonary hypertension rat models caused by different hypoxia protocols

Abstract

Background and aim: Pulmonary hypertension (PH) is a serious and even fatal disorder with limited treatment strategies. The hypoxia-induced pulmonary hypertension (HPH) rat model is commonly used in this field. While the HPH rat model has strong predictability and repeatability, the model is a chronic model, making it time-consuming, costly, and complicated and limiting the progress of the experiments. Currently, there is no uniform international standard for the HPH model. Our study aimed to find a relatively effective and efficient HPH modeling protocol. Methods: We established HPH rat models with different total hypoxia periods and different daily hypoxia times, and assessed different hypoxia modeling modes in multiple dimensions, such as haemodynamics, right ventricular (RV) hypertrophy, pulmonary arterial remodeling, muscularization, inflammation, and collagen deposition. Results: Longer daily hypoxia time resulted in higher mean pulmonary arterial pressure (mPAP)/right ventricular systolic pressure (RVSP) and more obvious RV hypertrophy, as well as more severe pulmonary arterial remodeling and muscularization, regardless of the total period of hypoxia (3- or 4-week). Moreover, pulmonary perivascular macrophages and collagen deposition showed daily hypoxia time-dependent increases, both in 3- and 4-week hypoxia groups. Conclusion: Our findings showed that the 3-week continuous hypoxia mode was a relatively efficient way to reduce the time needed to induce significant disease phenotypes, which offered methodological evidence for future studies in building HPH models.

Keywords:

• Collagen
• hypoxia
• modeling protocol
• pulmonary hypertension
• rat model

Acknowledgement

The authors thank the staff of Experimental Animal Center of Wenzhou Medical University for their guidance and help.

Disclosure statement

The authors report there are no competing interests to declare.

Ethical approval

All experiments in this study were approved by the Animal Ethics Committee of Wenzhou Medical University and performed in accordance with the ARRIVE guidelines and the Guide for the Care and Use of Laboratory Animals.

Data availability statement

The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Chinese National Natural Science Foundation (Grant numbers 82170061, 81873411).