FIGURE 4.

AT₁R signaling pathways activated by prolonged mechanical load or Ang II. The AT₁R is principally coupled to G_αq protein but is also coupled to G_αi protein through β-arrestin (β-arr) recruitment when the myocyte is subjected to mechanical load. Ang II- or stretch-induced G_αq signaling activates TRPC3/6 to initiate Ca²⁺ influx, which in turn activates calcineurin (CN)–NFAT pathway to promote pathological cardiac hypertrophy (red arrows). AT₁R–G_αi coupling induces EGFR transactivation and Akt/ERK phosphorylation, which promotes physiological hypertrophy and prosurvival signaling (blue arrows).