Rat as a model system for hypertension drug discovery

Polygenic ‘essential’ hypertension remains a leading risk factor for cardiovascular disease, strokes and chronic kidney disease. Current antihypertensive therapies successfully lower blood pressure but have not normalized the burden of hypertensive end-organ damage – be it cardiovascular, cerebrovascular or chronic kidney disease. Next-generation antihypertensives need to address the causal polygenic mechanisms, the subtype-specific heterogeneity and end-organ disease burden of polygenic ‘essential’ hypertension. Rat models of hypertension recapitulate the key features of human essential hypertension disease course such as the polygenic etiology, genetic subtypes, gene–environment interactions, exacerbation of end-organ damage through hypertension-common disease (atherosclerosis and diabetes) interactions and the spectrum of end-organ damage. As such, rat models of polygenic hypertension provide a strategic platform for preclinical testing of the safety and efficacy of next-generation antihypertensive therapies that target the normalization of blood pressure and ensuing end-organ damage.

Section editors:Ju Chen – University of California, San Diego, Department of Medicine, La Jolla, CA, USARobert Ross – University of California, San Diego, Cardiology Section, San Diego, CA, USA