Mgv. Petroff et al., Subcellular mechanisms of the positive inotropic effect of angiotensin II in cat myocardium, J PHYSL LON, 529(1), 2000, pp. 189-203
1. Cat ventricular myocytes loaded with [Ca2+](i)- and pH(i)-sensitive prob
es were used to examine the subcellular mechanism(s) of the Ang II-induced
positive inotropic effect. Ang II (1 muM) produced parallel increases in co
ntraction and Ca2+ transient amplitudes and a slowly developing intracellul
ar alkalisation. Maximal increases in contraction amplitude and Ca2+ transi
ent amplitude were 163 +/- 22 and 43 +/- 8%, respectively, and occurred bet
ween 5 and 7 min after Ang II administration, whereas pH(i) increase (0.06
+/- 0.03 pH units) became significant only 15 min after the addition of Ang
II. Furthermore, the inotropic effect of Ang II was preserved in the prese
nce of Na+-H+ exchanger blockade. These results indicate that the positive
inotropic effect of Ang II is independent of changes in pHi.
2. Similar increases in contractility produced by either elevating extracel
lular [Ca2+] or by Ang II application produced similar increases in peak sy
stolic Ca2+ indicating; that an increase in myofilament responsiveness to C
a2+ does not participate in the Ang II induced positive inotropic effect.
3. Ang II significantly increased the L-type Ca2+ current, as assessed by u
sing the perforated patch-clamp technique (peak current recorded at 0 mV: -
1.88 +/- 0.16 pA pF(-1) in control vs. -3.03 +/- 0.20 pA pF(-1) after 6-8 m
in of administration of Ang II to the bath solution).
4. The positive inotropic effect of Ang II was not modified in the presence
of either KB-R7943, a specific blocker of the Na+-Ca2+ exchanger, or ryano
dine plus thapsigargin, used to block the sarcoplasmic reticulum function.
5. The above results allow us to conclude that in the cat ventricle the Ang
II-induced positive inotropic effect is due to an increase in the intracel
lular Ca2+ transient, an enhancement of the L-type Ca2+ current being the d
ominant mechanism underlying this increase.