Reverse mode of the Na+-Ca2+ exchange after myocardial stretch - Underlying mechanism of the slow force response

This study was designed to gain additional insight into the mechanism of th e slow force response (SFR) to stretch of cardiac muscle. SFR and changes i n intracellular Na+ concentration ([Na+](i)) were assessed in cat papillary muscles stretched from 92% to approximate to 98% of L-max. The SFR was 120 +/-0.6% (n=5) of the rapid initial phase and coincided with an increase in [Na+](i). The SFR was markedly depressed by Na+-H+ exchanger inhibition, AT (1) receptor blockade, nonselective endothelin-receptor blockade and select ive ETA-receptor blockade, extracellular Na+ removal, and inhibition of the reverse mode of the Na+-Ca2+ exchange by KB-R7943. KB-R7943 prevented the SFR but not the increase in [Na+](i). Inhibition of endothelin-converting e nzyme activity by phosphoramidon suppressed both the SFR and the increase i n [Na+](i). The SFR and the increase in [Na+](i) after stretch were both pr esent in muscles with their endothelium (vascular and endocardial) made fun ctionally inactive by Triton X-100. In these muscles, phosphoramidon also s uppressed the SFR and the increase in [Na+](i). The data provide evidence t hat the last step of the autocrine-paracrine mechanism leading to the SFR t o stretch is Ca2+ entry through the reverse mode of Na+-Ca2+ exchange.