Modulation of the cardiac Na+/Ca2+ exchanger (NCX) by the endothelin-1-induced activation of the Na+/H+ exchanger (NHE).

VILLA-ABRILLE MC, AIELLO EA, CINGOLANI HE

Buenos Aires, Argentina

Congreso; XII Meeting of the ISHR Latin American Section; 2003

ISHR

Endothelin-1 (ET-1) is a potent positive inotropic peptide. However, the mechanisms involved are controversial. We evaluated the effects of ET-1 on the reversal potential (ENCX) of the NCX with whole-cell in cat ventricular myocytes. ET-1 produced a negative shift of ENCX (DENCX: ET-1 1 nM=-10±3 mV, ET-1 10 nM=-17±5 mV, n=12, P<0.05). This ENCX negative shift was prevented by the treatment of the cells with the blocker of the NHE, Cariporide (1 mM) (DENCX: ET-1 1 nM=2.1±3 mV, ET-1 10 nM=1.7±3.5 mV, n=8), indicating that it was possibly produced by the increase in Na+i induced by the stimulation of the NHE by ET-1. Accordingly, our results suggest that ET-1 induces the activation of the NHE, which increases Na+i, inducing an ENCX negative shift that favors the NCX reverse mode and promotes cell Ca2+ influx and a positive inotropic effect.