β-Arrestin-Biased AT₁ Agonist TRV027 Causes a Neonatal-Specific Sustained Positive Inotropic Effect Without Increasing Heart Rate.

ABSTRACT: The treatment of pediatric heart failure is a long-standing unmet medical need. Angiotensin II supports mammalian perinatal circulation by activating cardiac L-type Ca²⁺ channels through angiotensin type 1 receptor (AT₁R) and β-arrestin. TRV027, a β-arrestin-biased AT₁R agonist, that has been reported to be safe but not effective for adult patients with heart failure, activates the AT₁R/β-arrestin pathway. We found that TRV027 evokes a long-acting positive inotropic effect specifically on immature cardiac myocytes through the AT₁R/β-arrestin/L-type Ca²⁺ channel pathway with minimum effect on heart rate, oxygen consumption, reactive oxygen species production, and aldosterone secretion. Thus, TRV027 could be utilized as a valu

SUBMITTER: Kashihara T 

PROVIDER: S-EPMC7691286 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature