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 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.
de Hurtado
M C
MC
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Alvarez
B V
BV
Ennis
I L
IL
Cingolani
H E
HE
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000468:Alkalies / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism; D002021:Buffers; D002245:Carbon Dioxide / Q000378:metabolism; D002415:Cats; D027963:Chloride-Bicarbonate Antiporters; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008744:Methylamines / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D044022:Receptor, Endothelin A; D012964:Sodium / Q000502:physiology*
D000468:Alkalies; D017920:Antiporters; D001639:Bicarbonates; D002021:Buffers; D027963:Chloride-Bicarbonate Antiporters; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D008744:Methylamines; D009842:Oligopeptides; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D000804:Angiotensin II; D002245:Carbon Dioxide; C076213:PD 142893; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D012964:Sodium; C023336:trimethylamine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)