Influence of gender in monocrotaline and chronic hypoxia induced pulmonary hypertension in obese rats and mice

Abstract

Background Obesity and pulmonary hypertension (PH) share common characteristics, such as augmented inflammation and oxidative stress. However, the exact role of obesity in the pathology of PH is largely uninvestigated. Therefore, we have hypothesized that in the context of obesity the gender difference may have influence on development of PH in animal models of this disease. Methods Animal experiments were conducted in monocrotaline (MCT) and chronic hypoxia (HOX) models of PH. Lean and obese Zucker rats or B6 mice of both genders were used for MCT or HOX models, respectively. Echocardiography, hemodynamic measurements, histology and immuno-histochemistry were performed to analyze various parameters, such as right ventricular function and hypertrophy, hemodynamics, pulmonary vascular remodeling and lung inflammation. Results Both lean and obese male and female Zucker rats developed PH after a single MCT injection. However, negligible differences were seen between lean and obese male rats in terms of PH severity at the end stage of disease. Conversely, a more prominent and severe PH was observed in obese female rats compared to their lean counterparts. In contrast, HOX induced PH in lean and obese, male and female mice did not show any apparent differences. Conclusion Gender influences PH severity in obese MCT-injected rats. It is also an important factor associated with altered inflammation. However, further research is necessary to investigate and reveal the underlying mechanisms.

Upregulation of miR-335-5p Contributes to Right Ventricular Remodeling via Calumenin in Pulmonary Arterial Hypertension

“…Echocardiography was performed as previously described [ 17 ]. After anesthesia, the Vevo 2100 imaging system (Visual Sonics, Toronto, Canada) was used to obtain the echocardiographic images.…”

Experimental animal models of pulmonary hypertension: Development and challenges

“…49 An influence of gender on PH severity was seen in obese MCT-injected Zucker rats, and differences in MCT-induced developmental toxicity and fetal hepatotoxicity may contribute to the selective CYP3A induction in female fetuses. 50,51 Barrier-disruptive mechanisms may act as an earlier event in the MCT-PH model, increasing lung permeability related to early progression of PH in male rats than females. 52 SuHx-and MCT-induced PH models are the two main models used in PH with different pathophysiological characteristics: MCT-PH is associated with endothelial toxicity and marked by lung inflammation, while SuHx-PH is characterized by pulmonary vascular proliferative lesions such as the formation of neointimal plexiform lesions.…”

“…Recently, a novel MCT rat model was reported to be a good mimic of chronic neonatal PH characterized by reduced pulmonary microvascular growth, increased arterial muscularization, elevated RV systolic pressure, and RV hypertrophy 49 . An influence of gender on PH severity was seen in obese MCT‐injected Zucker rats, and differences in MCT‐induced developmental toxicity and fetal hepatotoxicity may contribute to the selective CYP3A induction in female fetuses 50,51 . Barrier‐disruptive mechanisms may act as an earlier event in the MCT‐PH model, increasing lung permeability related to early progression of PH in male rats than females 52 …”