Subcellular mechanisms of the positive inotropic effect of angiotensin II in cat myocardium
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 al...
Guardado en:
| Autores principales: | , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2000
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/127068 |
| Aporte de: |
| Sumario: | 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. |
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