| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
The heart has protective mechanisms against ischemia. Among them, ischemic preconditiong is a high-light. This protecting mechanism has been proposed to be mediated by intrinsic bioactive agents, such as adenosine, norepinephrine, angiotensin II, and endothelia. These substances unexceptionably activate the protein kinase C and the pertussis toxin (PTX)-sensitive GTP-binding proteins (Gi). In this study, we aimed to clarify the roles of the intrinsic agents in the ischemic preconditioning. Another cardio-protective mechanism is known in new-born hearts, which is termed as ischemic tolerance. We also examined the effects of adenosine on neonate myocytes in order to elucidate the role of the intrinsic factors in the myocardial protection in neonates. We first examine whether or not short-term hypoxia or NaCN (1mM) perfusion produces the ischemic preconditioning. Our results suggest that short-term ischemia does not induce the preconditioning effects. However, co-application of adenosine facilitates the activation of the ATP-sensitive K current. Thus, the ischemic preconditioning should be attributable to the intrinsic factors, not to ischemia itself. When compared between adult and neonate myocytes, adenosine showed a more potent inhibition of I_<Ca> in neonate myocytes than in adult cells. Therefore, this agent is considered to contribute not only to ischemic preconditioning but also to ischemic tolerance around birth. We also examined various intrinsic factors, which may contribute to the myocardial protection. We found that the stimulation of EP receptor by prostaglandin E1 or P2 receptor stimulation by ATP causes the stimulation of the perrutsis-sensitive G protein. Thus, these agents may contribute to IP in adult cells or ischemic tolerance in neonate ischemic tolerance.
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