ABSTRACT
Muchos de los efectos de la angiotensina II (Ang II) son mediados en realidad por la acción de endotelina (ET) endógena liberada y/o producida en respuesta a la Ang II. En este trabajo evaluamos la interacción Ang II/ET-1, sus consecuencias en la contractilidad cardíaca y el papel de las especies reactivas del oxígeno (EROs). Se usaron cardiomiocitos aislados de gato. La Ang II, 1 nM, produjo un efecto inotrópico positivo (EIP) de 31.8±3.8% que fue cancelado por inhibición de los receptores AT1, de los receptores de ET, del intercambiador Na+/H+ (NHE), del modo inverso del intercambiador Na+/Ca2+ (NCX) o por el secuestro de EROs. La Ang II, 100 nM, produjo un EIP de 70.5±7.6% que fue cancelado por inhibición de los receptores AT1y bloqueado en parte por inhibición de los receptores de ET, del NHE, del modo inverso del NCX o por el secuestro de EROs. La Ang II, 1 nM, incrementó el ARNm de la preproET-1 lo cual fue anulado por el bloqueo de los receptores AT1. Los resultados permiten concluir que el EIP de la Ang II es debido a la acción de la ET-1 endógena liberada/formada por la Ang II. La ET-1 produce: estimulación del NHE, activación del modo inverso del NCX y un consecuente EIP. Dentro de esta cascada también participarían los EROs.
Many of the effects thought to be due to angiotensin II (Ang II) are due to the release/formation of endothelin (ET). We tested whether Ang II elicits its positive inotropic effect (PIE) by the action of endogenous ET-1 and the role played by the reactive oxygen species (ROS) in this mechanism. Experiments were performed in cat isolated ventricular myocytes in which sarcomere shortening (SS) was measured to asses contractility after pharmacological interventions and the effect of Ang II on inotropism were analyzed. Ang II 1 nM increased SS by 31.8±3.8% (p<0.05). This PIE was cancelled by AT1 receptor blockade, by ET-1 receptors blockade, by Na+/H+ exchanger (NHE) inhibition, by reverse mode Na+/Ca2+ exchanger (NCX) blockade or by ROS scavenging. Ang II 100 nM increases SS by 70.5±7.6% (p<0.05). This PIE was completely abolished by AT1 receptors blockade and were partially bocked by ET-1 receptors blockade, by NHE inhibition, by reverse mode NCX blockade or by ROS scavenging. Ang II increased preproET-1 mRNA, effect that was blunted by AT1 receptors blockade. We conclude that Ang II induces (through its AT1 receptor) release/formation of ET-1, which acting in autocrine fashion on ET receptors of the isolated myocytes increases inotropism through NHE stimulation and NCX reverse mode activation. The participation of ROS is involved is this chain of events.