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PPARγ Agonist Rosiglitazone and Antagonist GW9662: Antihypertensive Effects on Chronic Intermittent Hypoxia-Induced Hypertension in Rats

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Abstract

The increased incidence of hypertension associated with obstructive sleep apnea (OSA) presents significant physical, psychological, and economic challenges. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in both OSA and hypertension, yet the therapeutic potential of PPARγ agonists and antagonists for OSA-related hypertension remains unexplored. Therefore, we constructed a chronic intermittent hypoxia (CIH)-induced hypertension rat model that mimics the pathogenesis of OSA-related hypertension in humans. The model involved administering PPARγ agonist rosiglitazone (RSG), PPARγ antagonist GW9662, or normal saline, followed by regular monitoring of blood pressure and thoracic aorta analysis using staining and electron microscopy. Intriguingly, our results indicated that both RSG and GW9662 appeared to potently counteract CIH-induced hypertension. In silico study suggested that GW9662's antihypertensive effect might mediated through angiotensin II receptor type 1 (AGTR1). Our findings provide insights into the mechanisms of OSA-related hypertension and propose novel therapeutic targets.

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Data Availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Abbreviations

AGTR1:

Angiotensin II receptor type 1

CIH:

Chronic intermittent hypoxia

DBP:

Diastolic blood pressure

GW:

GW9662

H&E:

Hematoxylin–eosin

NS:

Normal saline

Nx:

Normoxia

OSA:

Obstructive sleep apnea

PPARγ:

Peroxisome proliferator-activated receptor gamma

MPAP:

Pulmonary arterial pressure

Rg:

Radius of gyration

RMSD:

Root mean square deviation

RSG:

Rosiglitazone

MSAP:

Systemic arterial pressure

SBP:

Systolic blood pressure

TEM:

Transmission electron microscopy

TZDs:

Thiazolidinediones

EVG:

Verhoeff–Van Gieson elastic

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Funding

Funding This work was supported by the National Natural Science Foundation of China (82270456, 81970445).

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Author notes

  1. Ningzhi Zhang, Feng Wei and Sisi Ning contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China

    Ningzhi Zhang, Feng Wei, Jialu Hu, Hongtao Shi, Zhifeng Yao, Minna Tang, Yongqiao Zhang, Jiaxin Gong, Junbo Ge & Zhaoqiang Cui

  2. Department of Cardiology, Shanghai Changning Tianshan Traditional Chinese Medicine Hospital, Shanghai, China

    Sisi Ning

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  1. Ningzhi Zhang
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All institutional and national guidelines for the care and use of laboratory animals were followed and approved by Fudan University's Animal Ethics Committee, China.

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Zhang, N., Wei, F., Ning, S. et al. PPARγ Agonist Rosiglitazone and Antagonist GW9662: Antihypertensive Effects on Chronic Intermittent Hypoxia-Induced Hypertension in Rats. J. of Cardiovasc. Trans. Res. (2024). https://doi.org/10.1007/s12265-024-10499-6

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