Intracellular signaling following myocardial stretch: An autocrine/paracrine loop

The stretch of adult papillary muscle elicits a chain of autocrine/paracrine events in which the Na⁺/H⁺ exchanger (NHE-1) activation is the central step. This activation is induced by a sequential angiotensin II-endothelin (Ang II-ET) release and results in an increase in intracellular Na⁺ (Na_i ⁺) without significant changes in intracellular pH. The increase in Na_i ⁺ negatively shifts the reverse potential of the Na ⁺/Ca²⁺ exchanger (NCX) thus inducing cell Ca²⁺ influx that augments myocardial contractility. This increase in force represents the mechanical counterpart of the autocrine/paracrine mechanism triggered by stretch and has been called the slow force response (SFR) to stretch.