Subcellular mechanisms of the positive inotropic effect of angiotensin II in cat myocardium

• Autores: Vila Petroff, Martín Gerardo; Aiello, Ernesto Alejandro; Palomeque, Julieta; Salas, Margarita Ana; Mattiazzi, Alicia Ramona
• Año de publicación: 2000
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Ciencias Médicas; Ryanodine receptor; Internal medicine; Endocrinology; Inotrope; Contraction (grammar); Chemistry; Myocyte; Thapsigargin; Angiotensin ii; Contractility; Calcium
• Institución: Universidad Nacional de La Plata

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 and Ca²⁺] transient amplitudes and a slowly developing intracellular alkalisation. Maximal increases in contraction amplitude and Ca²⁺] transient amplitude were 163 ± 22 and 43 ± 8 %, respectively, and occurred between 5 and 7 min 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⁻¹ in control vs. -3·03 ± 0·20 pA pF⁻¹ after 6-8 min of administration of Ang II to the bath solution). 4 The positive inotropic effect of Ang II was not modified in the presence of either KB-R7943, a specific blocker of the Na⁺-Ca²⁺] exchanger, or ryanodine plus thapsigargin, used to block the sarcoplasmic reticulum function. 5 The above results allow us to conclude that in the cat ventricle the Ang II-induced positive inotropic effect is due to an increase in the intracellular Ca2+ transient, an enhancement of the L-type Ca²⁺] current being the dominant mechanism underlying this increase.
Centro de Investigaciones Cardiovasculares