Autocrine stimulation of cardiac Na+-Ca2+ exchanger currents by endogenous endothelin released by angiotensin II

The goal of the present study was to evaluate the effects of Ang II on the current produced by the Na+-Ca2+ exchanger (I-NCX) working in the reverse mode and the possible autocrine role played by, the release of endothelin (ET) in these actions. INCX was studied in isolation in cat cardiac myocytes. Angiotensin II (Ang 11) (100 nmol/L) increased I-NCX at potentials higher than 0 mV (at +60 mV: 2.07+/-0.22 pA/pF in control versus 2.73+/-0.22 pA/pF in Ang 11, n=9; P<0.05). The increase in I-NCX, induced by, Ang 11 was prevented by the treatment of the cells with the unspecific blocker of the ET receptors, TAK 044 (1 mumol/L) (at +60 mV: 2.15+/-0.27 pA/pF in control versus 2.01+/-0.26 pA/pF in Ang 11, n=5, NS). These results show, for the first time, that the effect of Ang H on I-NCX is the result of the autocrine actions of ET released by the octapeptide.