Impairment, altered function or altered requirements of various organs lead to corresponding changes of cardiovascular system, especially its central organ, the heart. The heart adapts to the altered conditions and requirements by intensive remodeling. The remodeling is usually very complex, including both structural (e.g. hypertrophy, fibrosis) and functional (e.g. electrophysiological, contractile remodeling) changes. The remodeling is initially compensatory and beneficial optimizing the pumping function but gradually it may become detrimental (heart failure, life-threatening arrhythmias). In this chapter we have focused on three experimental models, in which the heart is not targeted primarily, however the primary disease eventually affects the cardiovascular system significantly: diabetes mellitus, renal failure, and dysfunctional autonomic innervation. Rat models of these three conditions are described in detail with special focus on methodological aspects and experimental results obtained in our laboratory.