Effects of β‐adrenoceptor antagonists on Ca²⁺‐overload induced by lysophosphatidylcholine in rat isolated cardiomyocytes

Abstract

1 The effects of fl-adrenoceptor antagonists including (-)-and (+)-propranolol, (-)-and (+)-penbutolol, timolol, pindolol, atenolol, acebutolol and practolol on the Ca2+ -overload induced by lysophosphatidylcholine (LPC) were examined in isolated cardiomyocytes of the rat.2 Fura-2 was used for measurement of the intracellular calcium concentration ([Ca2+] 5 LPC markedly increased the release of creatine phosphokinase from 9 + 1 to 45 + 2% which could be significantly reduced by (-)-or (+)-propranolol but not by acebutolol or timolol. 6 The protective effects of (-)-and (+)-propranolol, (-)-and (+)-penbutolol against the Ca2+-overload induced by LPC were not associated with the fl-adrenoceptor antagonistic action, but probably with an unknown action which is related to the preservation of membrane integrity. Further studies are necessary to clarify the exact mechanisms of the protective action of these fl-adrenoceptor antagonists against the Ca2+-overload induced by LPC.

K‐7259: A Cardioprotective Derivative of Dilazep

“…It is of interest to note that some P-adrenoceptor antagonists (l-propranolol, dpropranolol, Z-penbutolol, and d-penbutolol; each at 20 pM) inhibit LPC (15 pM)-induced intracellular Ca2+ increase, cell-shape change, and release of creatine kinase, whereas other P-adrenoceptor antagonists (pindolol, timolol, atenolol, acebutolol, and practolol; each at 20 pM) and lidocaine (100 pM) do not inhibit the LPC (15 kM)-induced changes (6). It appears that P-adrenoceptor antagonistic action itself is not responsible for the protective action of P-adrenoceptor antagonists from the LPC-induced damage.…”

The role of β‐adrenergic receptors in the regulation of cardiac tolerance to ischemia/reperfusion. Why do β‐adrenergic receptor agonists and antagonists protect the heart?

“…Carvedilol can mitigate oxidative stress‐induced Ca 2+ overload of cardiomyocytes [69]. Propranolol alleviates lysophosphatidylcholine‐induced Ca 2+ overload of cardiomyocytes [70]. Since Ca 2+ overload and excessive ROS production plays an important role in I/R injury [6], it could be hypothesized that the cardioprotective effect of β‐AR antagonists in reperfusion of the heart could be mediated via inhibition of ROS production and a decrease in Ca 2+ overload.…”

Lipophilicity of Beta‐Adrenocepter Antagonists: A New Classification Scheme for Clinical Use

“…9 The pharmacodynamics, membrane stabilising activity and cardioprotective actions of beta-blockers depend on lipophilicity. 10,11 The central nervous system (CNS) adverse effects of betablockers (e.g. nightmares) are related to their hydrophobic nature, although these effects may not be exclusively due to lipophilicity.…”