An evaluation of cardiac health in the Spontaneously Hypertensive Rat Colony: Implications of evolutionary driven increases in concentric hypertrophy

Holjak, E. J. B. and Savinova, I. and Nelson, V. L. and Ogilvie, L. M. and Ng, A. M. and Edgett, B. A. and Platt, M. J. and Brunt, K. R. and Ask, K. and Simpson, J. A.

Am J Hypertens (2021) :

DOI: 10.1093/ajh/hpab155

Abstract

BACKGROUND: The Spontaneously Hypertensive Rat (SHR) Colony was established in 1963 and is the most commonly used rodent model for studying heart failure. Ideally, animal models should recapitulate the clinical disease as closely as possible. Any drift in a genetic model may create a new model that no longer adequately represents the human pathology. Further, instability overtime may lead to conflicting data between laboratories and/or irreproducible results. While systolic blood pressure is closely monitored during inbreeding, the sequelae of heart failure (e.g., cardiac hypertrophy) are not. Thus, the object of this review was to investigate whether the hypertension-induced sequelae of heart failure in the SHR have remained stable after decades of inbreeding. METHODS: A systematic review was performed to evaluate indices of cardiovascular health in the SHR over the past 60 years. For post hoc statistical analyses, studies were separated into 2 cohorts: Initial (mid - late 1900’s) and Current (early 2000’s - present) Colony SHRs. Wistar-Kyoto rats (WKY) were used as controls. RESULTS: Systolic blood pressure was consistent between Initial and Current Colony SHRs. However, Current Colony SHRs presented with increased concentric hypertrophy (i.e., elevated heart weight and posterior wall thickness) while cardiac output remained consistent. Since these changes were not observed in the WKY controls, cardiac-derived changes in Current Colony SHRs were unlikely due to differences in environmental conditions. CONCLUSIONS: Together, these data firmly establish a cardiac-based phenotypic shift in the SHR model and provide important insights into the beneficial function of concentric hypertrophy in hypertension-induced heart failure.

Citation

Holjak, E. J. B., Savinova, I., Nelson, V. L., Ogilvie, L. M., Ng, A. M., Edgett, B. A., Platt, M. J., Brunt, K. R., Ask, K., & Simpson, J. A. (2021). An evaluation of cardiac health in the Spontaneously Hypertensive Rat Colony: Implications of evolutionary driven increases in concentric hypertrophy. Am J Hypertens. https://doi.org/10.1093/ajh/hpab155 echocardiography, hemodynamics, cardiac remodelling, genetic drift, HFpEF

Keywords

• echocardiography
• hemodynamics
• cardiac remodelling
• genetic drift
• HFpEF