Stimulation of myocardial Na+-independent Cl--HCO(3)(-)exchanger by angiotensin II is mediated by endogenous endothelin

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.