© 2000 American Heart Association, Inc.
Cellular Biology |
Stimulation of Myocardial Na+-Independent Cl--HCO3- Exchanger by Angiotensin II Is Mediated by Endogenous Endothelin
From Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Correspondence to Dr Horacio E. Cingolani, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Calle 60 y 120, 1900 La Plata, Argentina.
Abstract—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+-independent Cl--HCO3- exchanger. Exposure to ET-1 (10 nmol/L) raised pHi by 0.13±0.03 U (P<0.05) in papillary muscles superfused with nominally HCO3--free solution, whereas no significant change was detected under CO2/HCO3--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, pHi increased by 0.09±0.02 U (P<0.05) in the presence of CO2/HCO3- buffer. The rate of pHi recovery from trimethylamine hydrochloride–induced intracellular alkaline load was enhanced so that net HCO3 efflux increased about three times in the presence of ET-1 (2.74±0.25 versus 9.66±1.29 mmol · L-1 · min-1 at pHi 7.55, P<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 ETA receptors). BQ 123 also abolished angiotensin II–induced activation of the Na+ independent Cl--HCO3- exchanger. These results show that ET-1 increases the activity of the Na+-independent Cl--HCO3- exchanger in cardiac tissue through the ETA receptors. Furthermore, our data suggest that the previously described angiotensin II–induced stimulation of the anion exchanger activity is mediated by endogenous ET-1.
Key Words: endothelin-1 • angiotensin II • anion exchanger • receptors, ETA • Na+-H+ exchanger
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