Cardiovascular disease (CVD) is the largest single cause of death in the UK, accounting for 35% of the total deaths every year [1]. A risk factor for heart failure is pathological cardiac hypertrophy, which is an irreversible pathological response to stress. Physiological hypertrophy, however, is reversible and can occur as a physiological adaptation to the greater cardiovascular demands of pregnancy and exercise. The mechanisms responsible for controlling the gene transcription required for the induction, maintenance and reversibility of the hypertrophic phenotype have not been fully clarified. Generation of the hypertrophic response is achieved through very intricate and complex signalling pathways. It is therefore difficult to distinguish the effects that the specific downstream-signalling pathways, the signal duration and the signal intensity play in the generation of the different forms of cardiac hypertrophy [2, 3]. We hypothesise that pathological hypertrophy is associated with transient exposure to hypertrophic stimuli and is sustained in the absence of the stimulus. We also hypothesise that physiological hypertrophy requires the presence of stimuli in order to persist, and is reversed upon removal. To test this hypothesis, primary cultures of neonatal rat (R. norvegicus) ventricular myocytes (NRVMs) were used as an in vitro model for cardiac hypertrophy. The pathological mediators, Endothelin-1 (ET-1) and BayK 8644, and the physiological mediator, Insulin-like growth factor-1 (IGF-1), were used to induce the hypertrophic phenotypes. Data obtained using RT-PCR shows that exposure to the pathological agonists, ET-1 and BayK 8644, stimulates significant fold increases in mRNA of the foetal genes, atrial natriuretic factor (ANF) and B-type natriuretic peptide (BNP), following 15 minute exposure when measured after 24 hours. Application of actinomycin D at the point of ET-1 removal prevented the induction of hypertrophic gene transcription. This indicates that the elevated levels of hypertrophic gene transcripts were due to continued transcription of the hypertrophic genes in the absence of ET-1 and were not due to the longevity of mRNA. ANF (but not BNP) expression was elevated following 30 minutes exposure to IGF-1 when measured after 24 hours. Interestingly, this effect of IGF-1 on ANF expression was sensitive to the ETA receptor antagonist, BQ123, suggesting an interaction between the two pathways. Further experiments hope to elucidate the temporal profile of ET-1 and IGF-1 induced hypertrophy. These data suggest that transient exposure to pathological and physiological agonists is sufficient to induce hypertrophy. The mechanism responsible for the maintenance of the hypertrophic response in the absence of the stimuli is yet to be elucidated.