Fig. 8.

Synthesis and actions of ET-1 in cardiomyocytes. Stretch, via angiotensin II (ANG II), stimulates ET-1 production. ET-1 can act in an autocrine manner to activate ET_A. This leads through several signaling pathways to increased Na⁺/H⁺ exchange activity which, in turn, activates Na⁺/Ca²⁺ exchange, thereby elevating [Ca²⁺]_i, leading to enhanced cell contraction. ET_B activation opposes this effect. Stretch, through as yet undefined mechanisms, stimulates ET-1 activation of ET_A which leads to increased ANP release. While components of the indicated pathways can regulate ANP production, there remains much uncertainty as to which signaling systems are predominantly involved in the ET-1 effect. See text for definitions.