Las especies reactivas del oxígeno son los mediadores intracelulares del aumento de la contractilidad cardíaca inducida por endotelina-1.

DE GIUSTI VC; CORREA MV; VILLA-ABRILLE MC; YEVES AM; CHIAPPE DE CINGOLANI GE; CINGOLANI HE; AIELLO EA

Buenos Aires, Argentina

Congreso; XV Congreso Argentino de Hipertension Arterial.; 2008

Sociedad Argentina de Hipertensión Arterial

Reactive oxygen species are the intracellular mediators of the increase in cardiac contractility induced by endothelin-1. De Giusti VC, Correa MV, Villa-Abrille MC, Yeves AM, Chiappe de Cingolani GE, Cingolani HE, Aiello EA. Centro de Investigaciones Cardiovasculares, Fac. de Cs. Médicas, UNLP, La Plata, Argentina. Reactive oxygen species (ROS) have been implicated in different deleterious cardiovascular actions. However, in recent years, it was shown that moderate concentrations of ROS can act as intracellular signaling molecules playing important roles in different physiological mechanisms. Thus, the objective of the present work was to evaluate the role and source of ROS generation in the positive inotropic effect of a physiological concentration of endothelin-1 (ET-1, 0.4 nM).  Isolated cat ventricular myocytes were used to measure sarcomere shortening with a video-camera, superoxide anion (.O2-) with chemiluminescence, and ROS production and intracellular pH (pHi) with epifluorescence.  The ET-1-induced positive inotropic effect (40.4±3.1 %, n=10, p<0.05) was associated to an increase in ROS production (105±29 fluorescence units above control, n=6, p<0.05). ET-1 also induced an increase in .O2- production that was inhibited by the NADPH oxidase blocker, apocynin, and by the blockers of mitochondrial ATP-sensitive K+ channels (mKATP), glibenclamide and 5 hydroxydecanoic acid. The ET-1-induced positive inotropic effect was inhibited by apocynin (0.3 mM; 6.3±6.6 %, n=13), glibenclamide (50 mM; 8.8±3.5 %, n=6), 5 hydroxydecanoic acid (500 mM; 14.1±8.1, n=9), and by scavenging ROS with MPG (2 mM; 0.92±5.6 %, n=8). The data suggest that ET-1 stimulates the NADPH oxidase, forming .O2- which opens mKATP and releases mitochondrial ROS, which in turn triggers an increase in contractility. These results show for the first time that mitochondrial ROS participate in the inotropic effects of ET-1 acting as intracellular signaling molecules.