TY - JOUR
T1 - Dissociation between positive inotropic and alkalinizing effects of angiotensin II in feline myocardium
AU - Mattiazzi, Alicia
AU - Perez, Néstor G.
AU - Vila-Petroff, Martín G.
AU - Alvarez, Bernardo
AU - Camilión De Hurtado, María C.
AU - Cingolani, Horacio E.
PY - 1997/3
Y1 - 1997/3
N2 - The present study examines the intracellular pH (pH(i)) dependence of angiotensin (ANG) II-induced positive inotropic effect in cat papillary muscles contracting isometrically (0.2 Hz, 30°C). Muscles were loaded with the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester for simultaneous measurement of pH(i) and contractility. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer (n = 4), there was a temporal dissociation between the positive inotropic and the alkalinizing effects of ANG II (0.5 μM). The positive inotropic effect of ANG II peaked at 9.7 ± 0.8 min (240 ± 57% above control) without significant changes in pH(i). The increase in pH(i) became significant (0.05 ± 0.01 pH units) only after 16 min of exposure to the drug, when the positive inotropic effect of ANG II was already fading. In HCO3/- buffer (n = 7), the ANG II-induced positive inotropic effect occurred without significant phi changes. In the presence of 5 μM ethyl isopropyl amiloride (EIPA, to specifically inhibit the Na+/H+ exchanger), the alkalinizing effect of ANG II was changed to a significant decrease in ph(i), despite which ANG II still increased contractility by 87 ± 16% (n = 6). The results indicate that in HEPES buffer only a fraction of the ANG II-induced positive inotropic effect can be attributed to a phi change, whereas in a physiological CO2-HCO3 medium the positive inotropic effect of ANG II is independent of phi changes. Furthermore, an ANG II-induced increase in myocardial contractility was observed even when ANG II administration elicited a decrease in pH(i), as occurred after Na+/H+ exchanger blockade. The results show that in feline myocardium, the increase in contractility evoked by ANG II in a physiological CO2-HCO3 medium is not due to an increase in Ca2+ myofilament sensitivity secondary to an increase in myocardial pH(i).
AB - The present study examines the intracellular pH (pH(i)) dependence of angiotensin (ANG) II-induced positive inotropic effect in cat papillary muscles contracting isometrically (0.2 Hz, 30°C). Muscles were loaded with the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester for simultaneous measurement of pH(i) and contractility. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer (n = 4), there was a temporal dissociation between the positive inotropic and the alkalinizing effects of ANG II (0.5 μM). The positive inotropic effect of ANG II peaked at 9.7 ± 0.8 min (240 ± 57% above control) without significant changes in pH(i). The increase in pH(i) became significant (0.05 ± 0.01 pH units) only after 16 min of exposure to the drug, when the positive inotropic effect of ANG II was already fading. In HCO3/- buffer (n = 7), the ANG II-induced positive inotropic effect occurred without significant phi changes. In the presence of 5 μM ethyl isopropyl amiloride (EIPA, to specifically inhibit the Na+/H+ exchanger), the alkalinizing effect of ANG II was changed to a significant decrease in ph(i), despite which ANG II still increased contractility by 87 ± 16% (n = 6). The results indicate that in HEPES buffer only a fraction of the ANG II-induced positive inotropic effect can be attributed to a phi change, whereas in a physiological CO2-HCO3 medium the positive inotropic effect of ANG II is independent of phi changes. Furthermore, an ANG II-induced increase in myocardial contractility was observed even when ANG II administration elicited a decrease in pH(i), as occurred after Na+/H+ exchanger blockade. The results show that in feline myocardium, the increase in contractility evoked by ANG II in a physiological CO2-HCO3 medium is not due to an increase in Ca2+ myofilament sensitivity secondary to an increase in myocardial pH(i).
KW - cat
KW - intracellular pH
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U2 - 10.1152/ajpheart.1997.272.3.h1131
DO - 10.1152/ajpheart.1997.272.3.h1131
M3 - Article
AN - SCOPUS:0030975755
SN - 0363-6135
VL - 272
SP - H1131-H1136
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3 41-3
ER -