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Titolo:
Protective effect of HOE642, a selective blocker of Na+-H+ exchange, against the development of rigor contracture in rat ventricular myocytes
Autore:
Ruiz-Meana, M; Garcia-Dorado, D; Julia, M; Inserte, J; Siegmund, B; Ladilov, Y; Piper, M; Tritto, FP; Gonzalez, MA; Soler-Soler, J;
Indirizzi:
Univ Vall Hebron, Gen Hosp, Serv Cardiol, E-08035 Barcelona, Spain Univ Vall Hebron Barcelona Spain E-08035 rdiol, E-08035 Barcelona, Spain Univ Giessen, Inst Physiol, Giessen, Germany Univ Giessen Giessen Germany iv Giessen, Inst Physiol, Giessen, Germany
Titolo Testata:
EXPERIMENTAL PHYSIOLOGY
fascicolo: 1, volume: 85, anno: 2000,
pagine: 17 - 25
SICI:
0958-0670(200001)85:1<17:PEOHAS>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
METABOLIC INHIBITION; REPERFUSION INJURY; INTRACELLULAR NA+; CARDIAC MYOCYTES; PH PARADOX; HEART; ISCHEMIA; SODIUM; ENERGY; CA2+;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Garcia-Dorado, D Univ Vall Hebron, Gen Hosp, Serv Cardiol, Paseo Vall Hebron 119-129, E-08035 Barcelona, Spain Univ Vall Hebron Paseo Vall Hebron 119-129 Barcelona Spain E-08035
Citazione:
M. Ruiz-Meana et al., "Protective effect of HOE642, a selective blocker of Na+-H+ exchange, against the development of rigor contracture in rat ventricular myocytes", EXP PHYSIOL, 85(1), 2000, pp. 17-25

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 mu M) 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. Ratiofluoresoence 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 transportersare inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations.

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Documento generato il 15/07/20 alle ore 21:32:09