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. 2020 Mar 13;11:181. doi: 10.3389/fphys.2020.00181

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Copyright © 2020 Seo, Parikh and Ashley.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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AT₁R downstream signaling pathways activated by acute stretch or Ang II. Membrane stretch directly or indirectly (by the autocrine release of Ang II) stimulates AT₁R which in turn activates distinct downstream signaling pathways: (1) ET_AR–EGFR–ERK1/2–NHE-1–NCX axis (red arrows) and (2) PLC–DAG–TRPC3/6 axis (blue arrows). The gradual influx of Ca²⁺ through NCX and TRPC3/6 channels enhances myocardial contractility, thereby initiating SFR. Ang II-triggered positive inotropic effect (PIE) shares the same pathways.