| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
|
|---|
| Research Abstract |
There are complicated interactions between active oxygens and autacoids and the influences of these interactions on the heart are modified significantly by the various pathophysiological conditions. Superoxide anion (O_2^-) constrict coronary artery resulting in increased release of nitric oxide (NO). The increased NO interact with O_2^- to form peroxynitrite (ONOO^-) and damages heart. Thus, although NO is protective in the case of reoxygenation injury, it is harmful when there are enormous amount of O_2^-. High concentration of hydrogen peroxide (H_2O_2) damages heart. However, when low concentration of H_2O_2 is coexist with O_2^-, H_2O_2 inhibits the O_2^--induced vasoconstriction by increasing the release of PGI_2. Which suppresses the increase in NO release, formation of ONOO^- and irreversible myocardial injury. The influence of O_2^- persist even after it has been washed out.Under the control condition, neither administration of NO nor inhibition of NO synthesis affects the profile of prostanoids release. However, when NO was administered after the O_2^- perfusion, NO induced coronary vasoconstriction. This paradoxical vasoconstriction is caused by the NO-induced increase in vasoconstricting prostanoids, such as PGF_<2alpha> and TXA_2. Inhibition of prostanoid synthesis with indomethacin reversed the NO-induced vasoconstriction to vasorelaxation. The interaction between NO and PGI_2 was also altered after hypoxia. Under the control condition, it was suggested that NO is more important than PGI_2 on the regulation of vascular tone, because inhibition of NO caused vasoconstriction, and inhibition of PGI_2 induced increased NO release. However, after the hypoxia, inhibition of NO resulted in increased release of PGI_2, and conversely, inhibition of PGI_2 synthesis suppressed NO release indicating that under the pathophysiological condition, NO synthesis is regulated by PGI_2.
|
