The slow force response to myocardial stretch is mediated by Ca2+ entry through the reverse mode of Na+-Ca2+ exchange, driven by an autocrine-paracrine mechanism.
The study provides evidence that the final step in the autocrine-paracrine mechanism leading to the slow force response to myocardial stretch is calcium entry through the reverse mode of the Na+-Ca2+ exchange.
This study was designed to gain additional insight into the mechanism of the slow force response (SFR) to stretch of cardiac muscle. SFR and changes in intracellular Na(+) concentration (Na(+)(i)) were assessed in cat papillary muscles stretched from 92% to approximately 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 selective ET(A)-receptor blockade, extracellular Na(+) removal, and inhibition of the reverse mode of the Na(+)-Ca(2+) exchange by KB-R7943. KB-R7943 prevented the SFR but not the increase in Na(+)(i). Inhibition of endothelin-converting enzyme activity by phosphoramidon suppressed both the SFR and the increase in Na(+)(i). The SFR and the increase in Na(+)(i) after stretch were both present in muscles with their endothelium (vascular and endocardial) made functionally inactive by Triton X-100. In these muscles, phosphoramidon also suppressed the SFR and the increase in Na(+)(i). The data provide evidence that the last step of the autocrine-paracrine mechanism leading to the SFR to stretch is Ca(2+) entry through the reverse mode of Na(+)-Ca(2+) exchange.
Pérez et al. (Fri,) conducted a other in Myocardial stretch. Myocardial stretch and pharmacological inhibition was evaluated on Slow force response (SFR) and changes in intracellular Na(+) concentration. The slow force response to myocardial stretch is mediated by Ca2+ entry through the reverse mode of Na+-Ca2+ exchange, driven by an autocrine-paracrine mechanism.