An Evaluation of Cardiac Health in the Spontaneously Hypertensive Rat Colony: Implications of Evolutionary Driven Increases in Concentric Hypertrophy.

Abstract

The Spontaneously Hypertensive Rat (SHR) Colony was established in 1963 and is the most commonly used rodent model for studying heart failure (HF). 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 (SBP) is closely monitored during inbreeding, the sequelae of HF (e.g., cardiac hypertrophy) are not. Thus, the object of this review was to investigate whether the hypertension-induced sequelae of HF in the SHR have remained stable after decades of inbreeding. 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 to late 1900s) and Current (early 2000s to present) Colony SHRs. Wistar-Kyoto rats (WKY) were used as controls. SBP 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. 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 HF.