Mcc. De Hurtado et al., Stimulation of myocardial Na+-independent Cl--HCO(3)(-)exchanger by angiotensin II is mediated by endogenous endothelin, CIRCUL RES, 86(6), 2000, pp. 622-627
Experiments were performed in isolated cat papillary muscles loaded with th
e pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in the
esterified form to study the effect of endothelin-1 (ET-I) on the activity
of the Na+-independent Cl--HCO3- exchanger. Exposure to ET-1 (10 nmol/L) r
aised 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 u
nder CO2/HCO3--buffered medium. However, if ET-1 was applied to muscles pre
treated with the anion exchanger inhibitor 4-acetamido-4'-isothiocyanato-st
ilbene-2,2'-disulfonic acid, pH(i) increased by 0.09+/-0.02 U (P<0.05) in t
he presence of CO2/HCO3- buffer. The rate of pH(i) recovery from trimethyla
mine 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 (n
onselective endothelin receptor blocker) or 300 nmol/L BQ 123 (selective bl
ocker of ETA receptors), BQ 123 also abolished angiotensin II-induced activ
ation of the Na+ independent Cl--HCO3- exchanger. These results show that E
T-1 increases the activity of the Na+-independent Cl--HCO3- exchanger in ca
rdiac tissue through the ETA receptors. Furthermore, our data suggest that
the previously described angiotensin II-induced stimulation of the anion ex
changer activity is mediated by endogenous ET-1.