Pestana-Oliveira Nayara, Nahey David B, Johnson Tim, Collister John P
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108, USA.
Bio Protoc. 2020 Aug 5;10(15):e3708. doi: 10.21769/BioProtoc.3708.
According to the World Health Organization (WHO), nearly 1.13 billion people worldwide have hypertension, a major factor responsible for premature death globally. The inherent multifactorial nature of hypertension makes its study difficult since the chronic rise in blood pressure depends on the intricate connection between dietary, genetic and environmental factors. Therefore, the pathophysi-ology of hypertension is not completely understood. For these reasons, there is an ongoing search for animal models that better mimic changes resulting from this disease. Because of its complexity, the use of animal models aimed at elucidating the pathogenesis of hypertension and to evaluate new therapeutic possibilities is an important tool for understanding this disease since it enables consistent experimental strategies that are impractical in humans. Over time, many animal models have been developed for the study of chronic increases in blood pressure ranging from genetic models that include the spontaneously hypertensive rat (SHR) and genetic manipulations, such as the TGR (mRen2) rat, as well as neurogenic or endocrine models. One of the most commonly used hypertensive rat models today is that of hypertension induced by treatment with deoxycorticosterone acetate associated with high sodium intake, , the DOCA-salt model. This model is known to have a neurogenic component linked to increased sympathetic nervous system activity, and as such the DOCA-salt model promotes cross-talk between endocrine and neural components that lead to increased blood pressure, and may impact the functioning of other organs.
根据世界卫生组织(WHO)的数据,全球近11.3亿人患有高血压,这是全球过早死亡的一个主要因素。高血压固有的多因素性质使其研究困难,因为血压的慢性升高取决于饮食、遗传和环境因素之间的复杂联系。因此,高血压的病理生理学尚未完全了解。出于这些原因,人们一直在寻找能更好模拟这种疾病所致变化的动物模型。由于其复杂性,使用旨在阐明高血压发病机制并评估新治疗可能性的动物模型是理解这种疾病的重要工具,因为它能实现一些在人类身上不切实际的一致实验策略。随着时间的推移,已经开发出许多动物模型用于研究血压的慢性升高,从包括自发性高血压大鼠(SHR)的遗传模型和基因操作(如TGR(mRen2)大鼠),到神经源性或内分泌模型。当今最常用的高血压大鼠模型之一是用醋酸脱氧皮质酮联合高钠摄入诱导的高血压模型,即DOCA-盐模型。已知该模型有一个与交感神经系统活动增加相关的神经源性成分,因此DOCA-盐模型促进了导致血压升高的内分泌和神经成分之间的相互作用,并且可能影响其他器官的功能。