Pharmacological characterization of isoproterenol-treated medaka fish

The transparent bodies of see-through medaka fish has led to their use as models for in vivo cell and tissue imaging. However, these fish may also prove useful as models for pathological processes. Accumulating reports show that pathology in fish is similar to that in mammals, including humans. In this study, pathological characterization, comparison of data from rodents and in vivo pharmacological analyses of isoproterenol (Iso)-treated fish were performed. Larval fish showed cardiac hypertrophy-like changes after exposure to > 10 microg/ml Iso for more than one day. Hearts of Iso-treated fish had a larger size and a thicker wall, especially in the ventricle, compared with normal hearts. Several messenger RNA levels dose-dependently increased in Iso-treated fish in a manner similar to that in rodents. Symptoms that accompany mammalian cardiac hypertrophy, such as congestion, were also observed. Propranolol (Pro), a non-selective beta-adrenoceptor blocker (AR), significantly protected the increase in heart rate and volume and other simultaneous symptoms induced by Iso exposure. Athletic capability, measured by optomotor response, showed a dose-dependent decrease after Iso treatment, but was protected by Pro. In contrast, metoprolol (Met) and butoxamine (Btx), selective beta1- and beta2-AR blockers, had little effect in this analysis. These results show that Iso-treated fish develop pathologies analogous to those found in mammalian systems, suggesting that medaka fish can be used for investigation of cardiac hypertrophy; however, drug affinity differences should be considered between species.