Top Things to Know: Animal Models of Hypertension
Published: March 14, 2019
- High blood pressure (hypertension/HTN) is the world’s most common chronic disease, causing substantial morbidity and mortality. There are a number of hypertension subtypes that exist along with the more common causes of hypertension. The precise cause of high blood pressure cannot often be determined in the clinical setting.
- Risk factors for primary (formerly called essential) hypertension include advanced aging, obesity, high dietary sodium intake, and low dietary potassium intake
- In hypertension, the utility of animal models for improving the understanding of the pathogenesis, prevention, and treatment of hypertension and its comorbidities depends on their validity for representing human forms of hypertension, including responses to therapy, and the quality of studies in those models.
- This paper describes several animal models used in hypertension research including large and small animals, platforms of experimental hypertension related to genetics, transgenic models, induced hypertension platforms, among others, with recommendations for using animal models of renovascular hypertension.
- Overweight and obesity contribute up to 75% of the risk for primary hypertension and to most cases of treatment-resistant hypertension. Although the physiological and molecular mechanisms of obesity-related hypertension remain elusive, sodium retention, renin-angiotensin-aldosterone system (RAAS) activation, increased sympathetic activity, leptin resistance, and endothelial dysfunction have been implicated. Understanding the mechanisms responsible for obesity-related hypertension may allow the development of novel strategies for treating these patients.
- Animal models that exhibit concomitant obesity and hypertension can be divided into 2 distinct categories: models of obesity that spontaneously develop hypertension and models of hypertension with superimposed obesity.
- Sex differences and aging in hypertension are among several areas in animal modeling for hypertension that are discussed in this paper and relate to the understanding of hypertension in humans.
- The impact of hypertension on human health occurs through end-organ damage to critical target organ systems, including the brain, heart, kidneys, and vasculature. Investigations of target organ damage in many established rodent models of hypertension have revealed insights into the mechanisms of BP-induced tissue injury. With the growing importance of comorbidities and aging in hypertension and its complications, studying aged animals and animals with induced comorbidities such as hyperglycemia, hyperlipidemia, and obesity would further increase the translational relevance of animal models of human hypertension.
- Investigations into target-organ damage in animal models of human hypertension have focused mainly on vessels, the heart, and the kidney, there is a lack of information on the brain effects in these models.
- Animal models of hypertension have been, and will likely remain, very useful in providing insights into the pathogenesis and novel treatment options of hypertension. This scientific statement is a comprehensive look at animal models used in hypertension research and how that research can be translated to humans. It also explores the gaps that need to be understood in order to develop better models for research in hypertension.
Citation
Lerman LO, Kurtz TW, Touyz RM, Ellison DH, Chade AR, Crowley SD, Mattson DL, Mullins JJ, Osborn J, Eirin A, Reckelhoff JF, Iadecola C, Coffman TM; on behalf of the American Heart Association Council on Hypertension and Council on Clinical Cardiology. Animal models of hypertension: a scientific statement from the American Heart Association [published online ahead of print March 14, 2019,]. Hypertension. doi: 10.1161/HYP.0000000000000090.