Ng. Perez et al., Reverse mode of the Na+-Ca2+ exchange after myocardial stretch - Underlying mechanism of the slow force response, CIRCUL RES, 88(4), 2001, pp. 376-382
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.