[Angiotensin II-induced endothelin-1 release in cardiac myocytes].
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.
Villa-Abrille
María C
MC
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina. mcvillaabrille@atlas.med.unlp.edu.ar
Cingolani
Horacio E
HE
Garciarena
Carolina D
CD
Ennis
Irene L
IL
Aiello
Ernesto A
EA
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D019332:Endothelin-1 / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010210:Papillary Muscles / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019332:Endothelin-1; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II