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. I_NCX was studied in isolation in cat cardiac myocytes. Angiotensin II (Ang II) (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 II, n = 9; P < 0.05). The increase in I_NCX induced by Ang II was prevented by the treatment of the cells with the unspecific blocker of the ET receptors, TAK 044 (1 μmol/L) (at +60 mV: 2.15±0.27 pA/pF in control versus 2.01±0.26 pA/pF in Ang II, n=5, NS). These results show, for the first time, that the effect of Ang II on I_NCX is the result of the autocrine actions of ET released by the octapeptide.