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Anesth Analg 2006;102:676-681
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000197780.42409.5b

CARDIOVASCULAR ANESTHESIA

Diazepam Enhances Inotropic Responses to Dopamine in Rat Ventricular Myocardium

María Jesús Juan-Fita, PhD, María Luisa Vargas, PhD, and Jesús Hernández, PhD

Departamento de Farmacologia, Facultad de Medicina, Murcia (Spain)

Address correspondence and reprint requests to Jesús Hernández, MD, PhD, Departmento de Farmacologia, Facultad de Medicina, Universidad de Murcia, Campus de Espinardo, 30071 Murcia, Spain. Address e-mail to jehernca{at}um.es

Diazepam inhibits phosphodiesterase type 4 and enhances the effect of some 3',5'-cyclic adenosine monophosphate (cAMP)-dependent positive inotropic drugs. We sought to determine whether diazepam and the selective phosphodiesterase type 4 inhibitor rolipram enhances the contractile response and cAMP levels induced by dopamine in rat myocardium. Dopamine (3–100 µM) produced concentration-dependent positive inotropic effects (–log EC50 = 5.21 ± 0.2, n = 5), which were augmented in the presence of 10 µM diazepam (-log EC50 = 5.40 ± 0.08, n = 6, P < 0.05) or 1 µM rolipram (-log EC50 = 5.41 ± 0.1, n = 6, P < 0.05). The effect of diazepam was not mimicked by 100 µM {gamma}-aminobutyric acid nor it was antagonized by a 5 µM concentration of the blockers of central and peripheral type benzodiazepine receptors, flumazenil and PK 11195. cAMP levels (pmol/g) produced by dopamine (744.4 ± 111.8, n = 5) in this tissue were enhanced by the presence of diazepam (1073 ± 97.7, n = 6, P < 0.05) or rolipram (1034.0 ± 245.2, n = 5, P < 0.05). Therefore, diazepam, like rolipram, augments the inotropic and biochemical effects of dopamine in rat myocardium. This effect is not mediated by benzodiazepine receptors but is probably the consequence of the phosphodiesterase type 4 inhibitory activity of diazepam.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.