| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Although angiotensin II is well known to cause hypertension and cardiac hypertrophy in the adult heart, it plays important roles in cardiovascular regulation in the perinatal period. I demonstrated previously that angiotensin II increases L-type Ca2+ channel activity through AT1 receptor/β-arrestin2 signaling in immature but not adult cardiomyocytes, suggesting that angiotensin II exerts a positive inotropic effect in the immature heart. Here I investigated the effect of TRV027, a β-arrestin-biased AT1 receptor agonist, on positive inotropic effect and its potential for pediatric heart failure using heart failure model mouse. TRV027 increased L-type Ca2+ channel activity and Ca2+ transient in immature cardiomyocytes through the same mechanism as angiotensin II. Experiments that treatment with TRV027 to mice with failing heart in the pediatric period showed that TRV027 had tendency to improve cardiac function of these mice.
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