Angiotensin II enhances cardiac Na+/Ca2+ exchanger current via an autocrine release of endothelin.

AIELLO EA, VILLA-ABRILLE MC, CINGOLANI HE.

Winnipeg, Canadá

Congreso; XVII ISHR World Congress of International Society for Heart Research; 2001

The influx of Ca2+ via the reverse mode of the Na+/Ca2+ exchanger might contribute to the increase in intracellular Ca2+ that activates myocardial contraction. The purpose of the present study was to evaluate the effects of angiotensin II (Ang II) on the current produced by the exchanger (INCX) working in the reverse mode (outward current). Whole-cell currents were measured in cat ventricular myocytes. INCX was identified by the application of the blockers of this current, KB-R4973 (5 mM) and Ni2+ (10 mM), which inhibited INCX the outward current registered at +60 mV by 46±11 % (n=5) and 80±7% (n=7), respectively. Ang II (100 nM) increased INCX at potentials higher than +10 mV (at +60 mV: 2.3±0.1 pA/pF in control vs 2.8±0.1 pA/pF in Ang II, n=17, p<0.05). No effects of Ang II were observed in the presence of Ni2+. Previous results obtained in cardiac multicellular preparations have shown that certain effects of Ang II are mediated by the release of endogenous endothelin (ET) (Cingolani et al., Circ Res. 83:775-780, 1998). Consistently, in the present study the increase in INCX induced by Ang II was prevented by the treatment of the myocytes with the blocker of the ET receptors, TAK044 (1 mM) (at +60 mV: 2.5±0.1 pA/pF in control vs 2.5±0.04 pA/pF in Ang II, n=13, NS). These results allow us to propose a mechanism by which Ang II stimulates the autocrine release of ET, which in turn promotes the increase in the activity of the reverse mode of the Na+/Ca2+ exchanger.