Camilión de Hurtado MC, Alvarez BV, Ennis IL, Cingolani HE. Stimulation of myocardial Na+-independent Cl--HCO3- exchanger by angiotensin II is mediated by endogenous endothelin

CAMILIÓN DE HURTADO MC; ALVAREZ BV; ENNIS IL; CINGOLANI HE

CIRCULATION RESEARCH

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2000 p. 622 - 627

0009-7330

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(-)-HCO(3)(-) exchanger. Exposure to ET-1 (10 nmol/L) raised pH(i) by 0.13+/-0.03 U (P<0.05) in papillary muscles superfused with nominally HCO(3)(-)-free solution, whereas no significant change was detected under CO(2)/HCO(3)(-)-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(i) increased by 0.09+/-0.02 U (P<0.05) in the presence of CO(2)/HCO(3)(-) buffer. The rate of pH(i) recovery from trimethylamine hydrochloride-induced intracellular alkaline load was enhanced so that net HCO(3) 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 pH(i) 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 ET(A) receptors). BQ 123 also abolished angiotensin II-induced activation of the Na(+) independent Cl(-)-HCO(3)(-) exchanger. These results show that ET-1 increases the activity of the Na(+)-independent Cl(-)-HCO(3)(-) exchanger in cardiac tissue through the ET(A) receptors. Furthermore, our data suggest that the previously described angiotensin II-induced stimulation of the anion exchanger activity is mediated by endogenous ET-1.