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Mecanismos subcelulares involucrados en el efecto inotrópico positivo y antirrelajante de la Angiotensina II y la Endotelina 1

Tesis

Autoría
VILA PETROFF, MARTIN GERARDO
Fecha
01/01/2003
Resumen Información suministrada por el agente en SIGEVA
SUMMARY 1. Cat ventricular myocytes loaded with Ca2+i and pHi sensitive probes were used to examine the subcellular mechanism/s of the Ang II-induced positive inotropic effect. Ang II (1 µM) produced parallel increases in contraction amplitude and Ca2+ transient and a slow developing intracellular alkalization. Maximal increases in contraction amplitude and Ca2+ transient amplitude were 263 ± 22 and 43 ± 8%, respectively and occured between 5 and 7 minutes after Ang II admin... SUMMARY 1. Cat ventricular myocytes loaded with Ca2+i and pHi sensitive probes were used to examine the subcellular mechanism/s of the Ang II-induced positive inotropic effect. Ang II (1 µM) produced parallel increases in contraction amplitude and Ca2+ transient and a slow developing intracellular alkalization. Maximal increases in contraction amplitude and Ca2+ transient amplitude were 263 ± 22 and 43 ± 8%, respectively and occured between 5 and 7 minutes after Ang II administration, whereas pHi increase (0.06 ± 0.03 pH units) became significant only 15 min after the addition of Ang II. Furthermore, the inotropic effect of Ang II was preserved in the presence of Na+/H+ exchanger blockade. These results indicate that the positive inotropic effect of Ang II is independent of changes in pHi. 2. Similar increases in contractility produced by either elevating extracellular Ca2+ or by Ang II application produced similar increases in peak systolic Ca2+ indicating that an increase in myofilament responsiveness to Ca2+ does not participate in the Ang II-induced positive inotropic effect. 3. Ang II significantly increased the L-type Ca2+ current, as assessed by using the perforated patch-clamp technique (Peak current recorded at 0 mV: -1.88 ± 0.16 pA/pF in control vs -3.03 ± 0.20 pA/pF after 6-8 minutes of administration of Ang II to the bath solution).
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Palabras Clave
Mecanismos subcelularesEndotelina 1Angiotensina IIefecto inotrópico positivo