Stimulation of Myocardial Na+-Independent Cl−-HCO3− Exchanger by Angiotensin II Is Mediated by Endogenous Endothelin
Experiments were performed in isolated cat papillary muscles loaded with the pH-sensitive dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in the esterified form to study the effect of endothelin-1 (ET-1) on the activity of the Na<sup>+</sup>-independent Cl<sup>−</sup>-H...
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| 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/10915/132989 |
| Aporte de: |
| Sumario: | Experiments were performed in isolated cat papillary muscles loaded with the pH-sensitive dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in the esterified form to study the effect of endothelin-1 (ET-1) on the activity of the Na<sup>+</sup>-independent Cl<sup>−</sup>-HCO<sub>3</sub><sup>−</sup> exchanger. Exposure to ET-1 (10 nmol/L) raised pH<sub>i</sub> by 0.13±0.03 U (<i>P</i><0.05) in papillary muscles superfused with nominally HCO<sub>3</sub><sup>−</sup>-free solution, whereas no significant change was detected under CO<sub>2</sub>/HCO<sub>3</sub><sup>−</sup>-buffered medium. However, if ET-1 was applied to muscles pretreated with the anion exchanger inhibitor 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonic acid, pH<sub>i</sub> increased by 0.09±0.02 U (<i>P</i><0.05) in the presence of CO<sub>2</sub>/HCO<sub>3</sub><sup>−</sup> buffer. The rate of pH<sub>i</sub> recovery from trimethylamine hydrochloride–induced intracellular alkaline load was enhanced so that net HCO<sub>3</sub> efflux increased about three times in the presence of ET-1 (2.74±0.25 versus 9.66±1.29 mmol · L<sup>−1</sup> · min<sup>−1</sup> at pH<sub>i</sub> 7.55, <i>P</i><0.05). This effect was canceled by previous exposure to either 50 nmol/L PD 142,893 (nonselective endothelin receptor blocker) or 300 nmol/L BQ 123 (selective blocker of ET<sub>A</sub> receptors). BQ 123 also abolished angiotensin II–induced activation of the Na<sup>+</sup> independent Cl<sup>−</sup>-HCO<sub>3</sub><sup>−</sup> exchanger. These results show that ET-1 increases the activity of the Na<sup>+</sup>-independent Cl<sup>−</sup>-HCO<sub>3</sub><sup>−</sup> exchanger in cardiac tissue through the ET<sub>A</sub> receptors. Furthermore, our data suggest that the previously described angiotensin II–induced stimulation of the anion exchanger activity is mediated by endogenous ET-1. |
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