Effects of acidosis on cardiotonic effect of forskolin

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Respiratory/metabolic acidosis is well known to reduce cardiotonic effect of catecholamines and PDE III inhibitors in animals. This investigation was designed to determine if cardiotonic effect of forskolin is influenced by lowered pH. Hydrochloric acid (2N) was continuously infused for approximately 1 hr to obtain pHa=7.4, 7.2 and 7.0 in 18 rats randomly assigned to three groups according to the pH. Then, forskolin was administered intravenously at 1, 3, and 6μg/kg/min for 1 hr. Forskolin increased CO, HR and Emax, and decreased SVR significantly and dose-dependently, but BP was not affected. Percent increase in CO and Emax by forskolin, however, was not influenced by pHa. In in vitro studies, pH of Hepes-Tyrode solution was adjusted at pH=7.4, 7.0, and 6.6 and forskolin was administered cumulatively, which increased isometric force of both right ventricle and left atrium significantly in a concentration-dependent manner. However, increases (%) in isometric force of both right ventricle and left atrium were not affected by pH. In addition, % changes in intracellular cAMP compared with vehicle (normal saline) application in both right ventricle and left atrium were similar at pH=7.4 and 6.6 after application of 10^<-3> M forskolin. These results indicate that the cardiotonic effect of forskolin is not affected by lowered pH, which is in clear contrast with catecholamines and PDE III inhibitors.