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

Abstract

The goal of the present study was to evaluate the effects of Ang II on the current produced by the Na<SUP>+</SUP>-Ca<SUP>2+</SUP> exchanger (I<SUB>NCX</SUB>) working in the reverse mode and the possible autocrine role played by the release of endothelin (ET) in these actions. I<SUB>NCX</SUB> was studied in isolation in cat cardiac myocytes. Angiotensin II (Ang II) (100 nmol/L) increased I<SUB>NCX</SUB> 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<SUB>NCX</SUB> 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<SUB>NCX</SUB> is the result of the autocrine actions of ET released by the octapeptide.