Endothelin-1 hypertrophic effect in neonatal rat cardiomyocytes: Involvement of Na+/H+ and Na+/Ca2+ exchangers

CAMILIÓN DE HURTADO MC; DULCE RA; HURTADO C; ÁLVAREZ MC; ENNIS IL; GARCIARENA CD; CALDIZ CB; PORTIANSKY EL; CHIAPPE DE CINGOLANI GE

Dallas, Texas EE.UU.

Congreso; 2005 Scientific Sessions of The American Heart Association; 2005

American Heart Association

Endothelin-1 (ET1) is a potent cell growth promoting agonist that stimulates Na+/H+ exchanger isoform 1 (NHE1) activity. The aim of this study was to explore the hypothesis that ET1-induced cardiomyocyte hypertrophy is mediated by a rise in intracellular Na+ concentration ([Na+]i) through NHE1 activation which in turn causes the reverse operation mode of  Na+/Ca2+ exchanger (NCXrev). In cultured neonatal rat cardiomyocytes 5 nmol/L ET1 induced cell hypertrophy as assessed by the increase in myocyte surface area, [3H]-phenylalanine incorporation and ANF mRNA expression (13 ± 2,  120 ± 12 and 90.2 ± 25.1 % over control, respectively, P< 0.05). These effects as well as the ET1-induced rise in [Na+]i (from 4.19 ± 1.29 to 8.05 ± 1.22 mmol/L, P < 0.05) were cancelled by NHE-1 inhibition with 1 ìmol/L HOE 642 (4.90 ± 1.43 mmol/L). Inhibition of NCXrev with 5 ìmol/L KB-R7943 significantly reduced the hypertrophic effect of ET1 (Figure 1). These results provide the first evidence that NCXrev is, secondarily to NHE-1 activation, involved in the development of ET1-induced cardiac hypertrophy