A New Approach for the Development of Multiple Cardiovascular Risk Factors in Two Rat Models of Hypertension

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.

Cardioprotective Effects of Aloysia polystachya Essential Oil on a Rat Model with Multiple Cardiovascular Risk Factors

“…Naïve cyteʼs cytoplasm [19]. Despite the EOAP being unable to reverse these alterations, we believe a chronic treatment associated with dietary changes could bring additional benefits to the model, which is a limitation of the current study.…”

“…This study employed a model of multiple cardiovascular risk factors to investigate the cardioprotective effects of EOAP in rats using rosuvastatin as control. Previously validated, this model associates dyslipidemia, hypothyroidism, and hypertension, inducing oxidative stress and cardiorenal impairments 19 . It is already well established that several risk factors, including dyslipidemia, hypertension, and hormonal modifications, are strongly related to higher cardiovascular risk outcomes 20 .…”

“…The experimental design for inducing multiple cardiovascular risk factors was developed by Moreno et al (2022) [19]. Male rats were randomized and divided into six experimental groups (n = 8/group): 1) naïve (Wistar-Kyoto rats; fed standard feed); 2) negative control (NC; SHR treated with filtered water 0.2 mL/ 100 g and fed high-fat diet (HFD)); 3) EOAP 1 (SHR treated with EOAP 1.47 mg/kg and feed with HFD); 4) EOAP 2 (SHR treated with EOAP 4.40 mg/kg and fed HFD); 5) EOAP 3 (SHR treated with EOAP 13.20 mg/kg and fed HFD); 6) ROSU (SHR treated with rosuvastatin 5 mg/kg and fed HFD).…”

Why Multitarget Vasodilatory (Endo)cannabinoids Are Not Effective as Antihypertensive Compounds after Chronic Administration: Comparison of Their Effects on Systemic and Pulmonary Hypertension

“…However, animal models are needed for preclinical studies to discover the specific genetic, cellular, and molecular mechanisms underlying the disease or to test novel therapeutic strategies. As the human pathophysiology of hypertension differs among individuals, it is difficult to create a model that ideally mimics all disturbances [28][29][30].…”

“…New methods are continuously being developed. For example, recently, two new models of rapid induction of multifactorial heart disease associated with hypertension (SHR and 2K1C), hypothyroidism, and a high-fat diet were introduced [30]. Similar to systemic hypertension, no single animal PH model is likely to be universally appropriate.…”