Rat models of hypertension, cardiac hypertrophy and failure (1998)

Introduction markedly increases with age [1] yet most models of hypertension and heart failure only use young adult rats.Animals have been used by humans for centuries to Animal models of ageing have been recently reviewed [2].understand their own biology.In cardiovascular research, Thirdly, the development of atherosclerosis is very unusual animal models have allowed the study of cardiovascular in most strains of rats, even in the presence of sustained disease in the early stages, as well as the investigation of high blood lipid levels, in contrast to humans where the mechanisms of the pathogenesis of cardiovascular atherosclerosis is common and an important risk factor in disease and the effects of drug intervention.The aim of hypertension and heart failure.these studies is to provide clear concepts for selected Although this review discusses almost exclusively exinvestigations in humans.An ideal animal model for any periments in living animals, such studies are not approcardiovascular disease in humans should have five charac-priate for all investigations of the cardiovascular system.teristics: (i) mimic the human disease, (ii) allow studies in Cell dispersion from adult hearts and the culture of chronic, stable disease, (iii) produce symptoms which are neonatal or adult cardiac fibroblasts or neonatal carpredictable and controllable, (iv) satisfy economical, tech-diomyocytes have replaced some animal studies since nical and animal welfare considerations, and (v) allow these allow studies of a single cell type in the absence of measurement of relevant cardiac, biochemical and haemo-homeostatic mechanisms over a wider range of experimendynamic parameters.tal conditions than easily obtained in vivo.However, while The use of rats as animal models is rational from the these studies have allowed characterisation of cell propeconomic viewpoint and many techniques have been erties, they cannot reproduce the working heart muscle.developed to measure relevant functional parameters.The use of animal models may be limited by ethical However, there is often insufficient consideration as to concerns and legislation, as a reaction to the diametrically whether the other criteria, especially the mimicry of human opposed opinions within the community on the necessity disease, are satisfied with the choice of rat models of for the use of animals in research [3].Some rats will cardiovascular disease.Three examples illustrate the prob-develop severe illness and death due to the procedures lems.Firstly, cardiovascular diseases such as hypertension described in this review; this is inevitable if these rats are and heart failure in humans are usually slowly developing valid models of human diseases with high morbidity and with wide-ranging neurohumoral adaptations in contrast to mortality.This review aims to present the commonly used the acute onset of symptoms in many surgical or drug-and some recently introduced rat models of hypertension, induced rat models of these important diseases.Secondly, cardiac hypertrophy and heart failure to allow rational cardiovascular disease is uncommon in young humans but discussion of the advantages and disadvantages of each model.