Protective effect of HOE642, a selective blocker of Na+-H+ exchange, against the development of rigor contracture in rat ventricular myocytes.

Abstract

The objective of this study was to investigate the effect of Na+-H+ exchange (NHE) and HCO3--Na+ symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re-energization (Rx). The effects of perfusion of HCO3- or HCO3--free buffer with or without the NHE inhibitor HOE642 (7 microM) were investigated during MI and Rx. In HCO3--free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 +/- 1% to 40 +/- 4% (P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx (P < 0.01). The presence of HCO3- abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca2+ (fura-2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na+ rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO3--dependent transporters are inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations.

• Authors: M Ruiz-Meana, D Garcia-Dorado, M Juliá, J Inserte, B Siegmund, Y Ladilov, M Piper, F P Tritto, M A González, J Soler-Soler
• Journal: Experimental physiology (Exp Physiol) Vol. 85 Issue 1 Pg. 17-25 (Jan 2000) ISSN: 0958-0670 [Print] England
• PMID: 10662888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bicarbonates
• Enzyme Inhibitors
• Guanidines
• Sodium-Hydrogen Exchangers
• Sulfones
• cariporide
• Sodium
• L-Lactate Dehydrogenase
• Calcium

Topics

• Animals
• Bicarbonates (metabolism)
• Calcium (metabolism)
• Energy Metabolism (physiology)
• Enzyme Inhibitors (pharmacology)
• Guanidines (pharmacology)
• Heart (drug effects)
• Heart Ventricles (cytology, drug effects, enzymology)
• Hydrogen-Ion Concentration
• In Vitro Techniques
• L-Lactate Dehydrogenase (metabolism)
• Male
• Myocardial Contraction (drug effects)
• Myocardium (cytology, enzymology)
• Perfusion
• Rats
• Rats, Sprague-Dawley
• Rigor Mortis (enzymology, prevention & control)
• Sodium (metabolism)
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Sulfones (pharmacology)