2003 Fiscal Year Final Research Report Summary
Effects of acidosis on cardiotonic effect of forskolin
| Project/Area Number |
14571418
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Akita University |
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Principal Investigator |
TANAKA Makoto Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (50236634)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Toshiaki Akita University, School of Medicine, Professor, 医学部, 教授 (50156048)
KIMURA Tetsu Akita University, School of Medicine, Research Associate, 医学部, 助手 (00312702)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Acidosis / Forskolin / Cardiotonic effect |
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| Research Abstract |
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.
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