A. Mattiazzi et al., DISSOCIATION BETWEEN POSITIVE INOTROPIC AND ALKALINIZING EFFECTS OF ANGIOTENSIN-II IN FELINE MYOCARDIUM, American journal of physiology. Heart and circulatory physiology, 41(3), 1997, pp. 1131-1136
The present study examines the intracellular pH (pH(i)) dependence of
angiotensin (ANG) II-induced positive inotropic effect in cat papillar
y muscles contracting isometrically (0.2 Hz, 30 degrees C). Muscles we
re loaded with the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carb
oxyfluorescein acetoxymethyl ester for simultaneous measurement of pH(
i) and contractility. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfoni
c acid (HEPES) buffer (n = 4), there was a temporal dissociation betwe
en the positive inotropic and the alkalinizing effects of ANG II (0.5
mu M) The positive inotropic effect of ANG II peaked at 9.7 +/- 0.8 mi
n (240 +/- 57% above control) without significant changes in pH(i), Th
e increase in pH(i) became significant (0.05 +/- 0.01 pH units) only a
fter 16 min of exposure to the drug, when the positive inotropic effec
t of ANG II was already fading. In HCO, buffer (n = 7), the ANG II-ind
uced positive inotropic effect occurred without significant pH(i) chan
ges. In the presence of 5 mu M ethyl isopropyl amiloride (EIPA, to spe
cifically inhibit the Na+/H+ exchanger), the alkalinizing effect of AN
G II was changed to a significant decrease in pH(i), despite which ANG
II still increased contractility by 87 +/- 16% (n = 6). The results i
ndicate that in HEPES buffer only a fraction of the ANG II-induced pos
itive inotropic effect can be attributed to a pH(i) change, whereas in
a physiological CO2-HCO3- medium the positive inotropic effect of ANG
II is independent of pH(i) changes. Furthermore, an ANG II-induced in
crease in myocardial contractility was observed even when ANG II admin
istration elicited a decrease in pH(i), as occurred after Na+/H+ excha
nger blockade. The results show that in feline myocardium, the increas
e in contractility evoked by ANG II in a physiological CO2-HCO3- mediu
m is not due to an increase in Ca2+ myofilament sensitivity secondary
to an increase in myocardial pH(i).