Diazepam potentiates the effects of endogenous catecholamines on contractility and cyclic AMP levels in rat ventricular myocardium

Naunyn-Schmiedeberg's Archives of Pharmacology
J Marín, J Hernández

Abstract

Diazepam has phosphodiesterase (PDE) inhibitory activity and potentiates the effect of some 3',5'-cyclic adenosine monophosphate (cAMP)-dependent positive inotropic agents. The present study was undertaken to determine whether diazepam enhances the contractile responses and cAMP levels induced by endogenous catecholamines in electrically driven rat right ventricular strips, and the effects are compared with that of the PDE inhibitor 3-isobutylmethylxantine (IBMX). Noradrenaline (10 nM(-1) microM), adrenaline (50 nM-500 microM) and tyramine (5-100 microM) produced concentration-dependent positive inotropic effects that were potentiated by the presence of 10 microM diazepam or IBMX. The diazepam-induced potentiation of the contractile effect of the sympathomimetic agents was not mimicked by 100 microM GABA nor was it antagonized by a 5 microM concentration of the blockers of central and peripheral type benzodiazepine receptors, flumazenil and PK 11195. The beta(2)-adrenergic receptor agonist salbutamol (0.1-300 microM) also produced a concentration-dependent positive inotropic effect which was potentiated by the presence of 10 microM diazepam or 10 microM IBMX. However, the contractile effect of salbutamol, either alone or in the...Continue Reading

Citations

Jun 29, 2004·Clinical Therapeutics·Maria D CarcelesJesús Hernández
Feb 24, 2006·Anesthesia and Analgesia·María Jesús Juan-FitaJesús Hernández

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