Angiotensin II Activates Na+-Independent Cl--HCO3- Exchange in Ventricular Myocardium

• Published in: Circulation research 1998-03, Vol.82 (4), p.473-481
• Main Authors: de Hurtado, Maria C. Camilion, Alvarez, Bernardo V, Perez, Nestor G, Ennis, Irene L, Cingolani, Horacio E
• Format: Article
• Language: English
• Subjects: Alkaloids; Amiloride - analogs & derivatives; Amiloride - pharmacology; Angiotensin II - physiology; Angiotensin Receptor Antagonists; Animals; Antiporters - metabolism; Benzophenanthridines; Bicarbonates - metabolism; Biological and medical sciences; Cats; Chloride-Bicarbonate Antiporters; Chlorides - metabolism; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Heart; Heart Ventricles - metabolism; Hydrogen-Ion Concentration; In Vitro Techniques; Losartan - pharmacology; Myocardium - metabolism; Phenanthridines - pharmacology; Protein Kinase C - antagonists & inhibitors; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Signal Transduction; Sodium - metabolism; Sodium-Hydrogen Exchangers - antagonists & inhibitors; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.82.4.473

The effect of angiotensin II (Ang II) on the activity of the cardiac Na Cl3 exchanger (anionic exchanger [AE]) was explored in cat papillary muscles. pHi was measured by epifluorescence with BCECF-AM. Ang II (500 nmol/L) induced a 5-(N-ethyl-N-isopropyl)amiloride-sensitive increase in pHi in the absence of external HCO3 (HEPES buffer), consistent with its stimulatory action on Na exchange (NHE). This alkalinizing effect was not detected in the presence of a CO2-HCO3 buffer (pH (i) 7.07 +/- 0.02 and 7.08 +/- 0.02 before and after Ang II, respectively; n=17). Moreover, in Na HCO3 medium, in which neither NHE nor Na3 cotransport are acting, Ang II decreased pHi, and this effect was canceled by previous treatment with SITS. These findings suggested that the Ang II-induced activation of NHE was masked, in the presence of the physiological buffer, by a HCO3 acidifying mechanism, probably the AE. This hypothesis was confirmed on papillary muscles bathed with HCO3 buffer that were first exposed to 1 [micro sign]mol/L S20787, a specific inhibitor of AE activity in cardiac tissue, and then to 500 nmol/L Ang II (n=4). Under this condition, Ang II increased pHi from 7.05 +/- 0.05 to 7.22 +/- 0.05 (P