Subcellular mechanisms of the positive inotropic effect of angiotensin II in cat myocardium

J Physiol. 2000 Nov 15;529 Pt 1(Pt 1):189-203. doi: 10.1111/j.1469-7793.2000.00189.x.

Abstract

1. Cat ventricular myocytes loaded with [Ca2+]i- and pHi-sensitive probes were used to examine the subcellular mechanism(s) of the Ang II-induced positive inotropic effect. Ang II (1 microM) produced parallel increases in contraction and Ca2+ transient amplitudes and a slowly developing intracellular alkalisation. Maximal increases in contraction amplitude and Ca2+ transient amplitude were 163 +/- 22 and 43 +/- 8 %, respectively, and occurred between 5 and 7 min after Ang II administration, whereas pHi 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 presence 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 extracellular [Ca2+] or by Ang II application produced similar increases in peak systolic Ca2+ indicating that an increase in myofilament responsiveness to Ca2+ does not participate in the Ang II-induced positive inotropic effect. 3. Ang II significantly increased the L-type Ca2+ current, as assessed by using 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 min 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 ryanodine 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 intracellular Ca2+ transient, an enhancement of the L-type Ca2+ current being the dominant mechanism underlying this increase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Angiotensin II / pharmacology*
  • Animals
  • Calcium Channels / drug effects
  • Calcium Channels / physiology
  • Cardiotonic Agents / pharmacology*
  • Cats
  • Electrophysiology
  • Fluorescent Dyes
  • Heart / drug effects*
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Indoles
  • Membrane Potentials / physiology
  • Myocardial Contraction / drug effects*
  • Myocardium / ultrastructure
  • Patch-Clamp Techniques
  • Sarcoplasmic Reticulum / physiology
  • Sodium-Calcium Exchanger / metabolism
  • Subcellular Fractions / drug effects*

Substances

  • Calcium Channels
  • Cardiotonic Agents
  • Fluorescent Dyes
  • Indoles
  • Sodium-Calcium Exchanger
  • Angiotensin II
  • indo-1