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 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.
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
N G
NG
Pérez
M C
MC
de Hurtado
H E
HE
Cingolani
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002415:Cats; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006020:Glycopeptides / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000502:physiology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019831:Sodium-Calcium Exchanger / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D006020:Glycopeptides; D018398:Homeodomain Proteins; D010456:Peptides, Cyclic; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; C088196:TAK 044; D008666:Metalloendopeptidases; C008890:phosphoramidon