Comparative actions of diazepam and other phosphodiesterase inhibitors on the effects of noradrenaline in rat myocardium.
Diazepam inhibits different isoforms of the enzyme cyclic nucleotide phosphodiesterase and also potentiates the inotropic effect of endogenous catecholamines in rat heart. In the present study we have examined whether this late effect is the consequence of inhibition of a phosphodiesterase subtype or whether inhibition of several phosphodiesterase subtypes is involved. We compared the effect of diazepam with that of the selective inhibitors of phosphodiesterase1 (MIMX), phosphodiesterase2 (EHNA), phosphodiesterase3 (milrinone) and phosphodiesterase4 (rolipram) on the inotropic effect of noradrenaline in rat ventricle. Both rolipram or diazepam were equipotent and more effective than milrinone in potentiating the inotropic effect of noradrenaline whereas EHNA and MIMX had no effect. The results suggest that the diazepam induced potentiation of the contractile effect of noradrenaline is due principally to inhibition of phosphodiesterase4 isoenzyme activity.
Juan-Fita
María J
MJ
Department of Pharmacology, Faculty of Medicine, Campus de Espinardo, Murcia, Spain.
Vargas
María L
ML
Hernández
Jesús
J
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D020105:Milrinone / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C119531:8-methoxymethyl-3-isobutyl-1-methylxanthine; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; C010192:9-(2-hydroxy-3-nonyl)adenine; D000242:Cyclic AMP; D000225:Adenine; D020105:Milrinone; D020889:Rolipram; D003975:Diazepam; D009638:Norepinephrine