Dissociation between the positive inotropic and alkalinizing
effects of angiotensin ii in feline myocardium.
Alicia, Mattiazzi, Perez N[acute]estor G., Vila-Petroff Mart[acute]in
G., Alvarez Bernardo, Camili[acute]on De Hurtado Mar[acute]ia C. and
Cingolani Horacio E.
Centro de Investigaciones Cardiovasculares, Calle 60 y 120,
Facultad de Ciencias M[acute]edicas, 1900 La Plata, Argentina
APStracts 3:0440H, 1996.
The present study examines the pHi-dependence of Ang?II-induced
positive inotropic effect in cat papillary muscles contracting
isometrically (0.2 Hz, 30 degrees C). Muscles were loaded with the
fluorescent dye BCECF-AM for simultaneous measurement of
intracellular pH (pHi) and contractility. In HEPES buffer (n=4),
there was a temporal dissociation between the positive inotropic and
the alkalinizing effect of Ang?II (0.5 [mu]M): The positive inotropic
effect of Ang?II peaked at 9.7 +/- 0.8 min (240 +/- 57% above
control) without significant changes in pHi. The increase in pHi
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 bicarbonate buffer (n=7), the Ang?II-induced
positive inotropic effect occurred without significant pHi changes.
In the presence of 5 [mu]M EIPA, to specifically inhibit the Na+/H+
exchanger, the alkalinizing effect of Ang?II was changed to a
significant decrease in pHi, in spite of 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 physiologic
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 pHi as occurred after Na+/H+ exchanger
blockade. The results show that in feline myocardium, the increase in
contractility evoked by Ang II in a physiologic CO2/HCO3- medium, is
not due to an increase Ca2+ myofilament sensitivity secondary to an
increase in myocardial pHi.
Received 12 March 1996; accepted in final form 17 September 1996.
APS Manuscript Number H240-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996