TY - JOUR
T1 - Stimulation of myocardial Na+-independent Cl-HCO3- exchanger by angiotensin II is mediated by endogenous endothelin
AU - Camilión De Hurtado, Maria C.
AU - Alvarez, Bernardo V.
AU - Ennis, Irene L.
AU - Cingolani, Horacio E.
PY - 2000/3/31
Y1 - 2000/3/31
N2 - 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 pH(i) 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, pH(i) 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 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-HCO3- exchanger. These results show that ET-1 increases the activity of the Na+-independent Cl-HCO3- 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.
AB - 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 pH(i) 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, pH(i) 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 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-HCO3- exchanger. These results show that ET-1 increases the activity of the Na+-independent Cl-HCO3- 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.
KW - Angiotensin II
KW - Anion exchanger
KW - Endothelin-1
KW - Na-H exchanger
KW - Receptors, ET(A)
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U2 - 10.1161/01.res.86.6.622
DO - 10.1161/01.res.86.6.622
M3 - Article
C2 - 10746996
AN - SCOPUS:0034737643
SN - 0009-7330
VL - 86
SP - 622
EP - 627
JO - Circulation research
JF - Circulation research
IS - 6
ER -