A New Animal Model to Study Endogenous Cardiotonic Steroids and the Progression of Cardiovascular Events in Salt-Sensitive Hypertension

Abstract

The Dahl salt-sensitive rat is a well-established model to study essential hypertension. We first described a subgroup of these rats based on the unique response pattern in systolic blood pressure during the first weeks of exposure to a high salt diet that included cataract formation. We classified this group as cataract-prone Dahl salt-sensitive rat. We also were able to predict and prevent cataract formation in these rats. Further studies showed an inhibition of lens Na, K-ATPase activity which may be in part responsible for the cataract formation. Other studies in Dahl salt-sensitive rats maintained on a high salt diet have also shown decreased Na, K-ATPase activity in several tissues and increased levels of endogenous circulating Na, K pump inhibitors. For over 20 years, endogenous cardiotonic steroids have been postulated to inhibit Na, K-ATPase in both humans as well as in experimental animal models of hypertension. Recent findings have shown results suggesting that there are several forms of cardiotonic steroids with minor differences in structural functionalities, site of production, and specific pump selectivity. We present original data that supports a role for cardiotonic steroids in disease progression related to increased salt-sensitivity. We found increased levels of free endogenous cardiotonic steroids in those rats that were classified as cataract-prone according to their initial systolic blood pressure response to a high salt intake when compared to non-cataract prone Dahl salt-sensitive rats and their control Dahl salt-resistant rats. The cataract-prone Dahl salt-sensitive rat is an animal model that can help and contribute to open a new door to possibly elucidate the role of endogenous cardiotonic steroids in the pathogenesis and progression of diseases related to salt-sensitive hypertension.