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A New Approach for the Development of Multiple Cardiovascular Risk Factors in Two Rat Models of Hypertension
Karyne Garcia Tafarelo Moreno1, Aline Aparecida Macedo Marques1, Gabriela Pereira da Silva1
1Laboratory of Cardiovascular Pharmacology (LaFAC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil.
Insights
Researchers developed a new animal model for cardiovascular disease (CVD) using hypertension, hypothyroidism, and a high-fat diet. This model effectively mimics human CVD risk factors and associated pathophysiological changes.
Area of Science:
- Cardiovascular research
- Animal modeling
- Non-communicable diseases
Background:
- Cardiovascular disease (CVD) is a leading cause of death globally.
- Existing animal models often fail to replicate the complex interplay of multiple human cardiovascular risk factors.
- A validated model is crucial for understanding and treating multifactorial CVD.
Purpose of the Study:
- To develop and validate a novel animal model incorporating hypertension, hypothyroidism, and a high-fat diet (HFD).
- To assess the efficacy of two hypertension models (2K1C and SHRs) in mimicking human CVD conditions.
- To evaluate the combined impact of these risk factors on cardiovascular and organ health.
Main Methods:
- Induction of renovascular hypertension (2K1C) and use of spontaneously hypertensive rats (SHRs).
- Thyroidectomy followed by a 6-week high-fat diet (HFD) administration.
- Comprehensive analysis including renal function, serum markers, ECG, blood pressure, vascular reactivity, and histopathology.
Main Results:
- Both models demonstrated dyslipidemia, impaired renal function, and hepatic steatosis.
- Elevated inflammatory markers and oxidative stress were observed in both experimental groups.
- Hypertensive rats exhibited significant end-organ damage, with SHRs showing more pronounced pathophysiological alterations.
Conclusions:
- The developed animal model effectively replicates multiple human cardiovascular risk factors and associated pathologies.
- This model provides a viable alternative for studying complex, multifactorial cardiovascular disease.
- Spontaneously hypertensive rats (SHRs) presented a more severe phenotype, offering a robust platform for CVD research.
Abstract:
Cardiovascular disease (CVD) is the leading cause of death among non-communicable diseases. There is a lack of valid animal models that mimic associations among multiple cardiovascular risk factors in humans. The present study developed an animal model that uses multiple cardiovascular risk factors-namely, hypertension, hypothyroidism, and a high-fat diet (HFD). Two models of hypertension were used: renovascular hypertension (two-kidney, one clip [2K1C]) and spontaneously hypertensive rats (SHRs). The naive group was composed of normotensive rats. Twelve weeks after surgery to induce renovascular hypertension, rats in the 2K1C and SHR groups underwent thyroidectomy. The HFD was then implemented for 6 weeks. Renal function, serum redox status, biochemical CVD markers, electrocardiographic profile, blood pressure, mesenteric vascular bed reactivity, histopathology, and morphometry were investigated. Both experimental models induced dyslipidemia, renal function impairment, and hepatic steatosis, accompanied by higher levels of different inflammatory markers and serum oxidative stress. These alterations contributed to end-organ damage in all hypertensive rats. Our findings corroborate a viable alternative model that involves multiple cardiovascular risk factors and resembles conditions that are seen in humans. Both models mimicked CVD, but our data show that SHRs exhibit more significant pathophysiological changes.
