title: Inotropic responses to phosphodiesterase inhibitors in cardiac hypertrophy in rats.
abstract: In the present study we sought to determine whether reduced contractile responses to phosphodiesterase inhibitors occur in the face of chronic cardiac hypertrophy associated with beta-adrenergic inotropic downregulation. As compared to age-matched Wistar-Kyoto control rats, spontaneously hypertensive rats at 6-8 months of age exhibited a striking decrease in left ventricular inotropic responses induced by isoproterenol, a beta-adrenoceptor agonist, in isolated, isovolumically contracting heart preparations. Despite profound beta-adrenoceptor-mediated inotropic downregulation, similar contractile responses to the phosphodiesterase III selective inhibitors, amrinone and milrinone, the phosphodiesterase IV selective inhibitor, rolipram, and non-selective phosphodiesterase inhibitor, pentoxifylline, were detected in normal and hypertrophic heart preparations. Moreover, the inotropic potency of the cAMP analogue, 8-Br-cAMP, was increased in spontaneously hypertensive rats. These findings suggest that in chronic cardiac hypertrophy, contractile responses to phosphodiesterase inhibitors may be preserved despite marked reductions in inotropic responses to beta-adrenoceptor agonists.
authors.affiliation: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, Johannesburg 2193, South Africa. woodiwissaj@physiology.wits.ac.za
authors.forename: Oleg
authors.initials: O
authors.lastname: Osadchii
authors.forename: Gavin
authors.initials: G
authors.lastname: Norton
authors.forename: Angela
authors.initials: A
authors.lastname: Woodiwiss
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000676:Amrinone / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D010431:Pentoxifylline / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020889:Rolipram / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000676:Amrinone; D020889:Rolipram; D007545:Isoproterenol; D010431:Pentoxifylline