title: Cardiovascular effects of BRX-005 comparison to bimoclomol.
abstract: Concentration-dependent effects of BRX-005, the novel heat shock protein coinducer, cardioprotective and vasoprotective agent, on intracellular calcium transients and contractility were studied in Langendorff-perfused guinea pig hearts loaded with the fluorescent calcium indicator dye Fura-2. BRX-005 increased peak left ventricular pressure, the rate of force development and relaxation significantly in a concentration-dependent manner. The amplitude of [Ca2+]i transients was left unaltered by the drug. In contrast to BRX-005, bimoclomol increased both contractility and the amplitude of [Ca2+]i transients. In canine ventricular cardiomyocytes high concentrations of BRX-005 had no effect on depolarization, whereas bimoclomol suppressed action potential upstroke markedly. In guinea pig pulmonary artery preparations precontracted with phenylephrine, BRX-005 induced concentration-dependent relaxation. This effect of BRX-005 was independent of the integrity of endothelium indicating that vasorelaxant effect of the drug develops directly on vascular smooth muscle.
authors.affiliation: Department of Physiology, University Medical School of Debrecen, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Körtvély
authors.forename: G
authors.initials: G
authors.lastname: Szigeti
authors.forename: R
authors.initials: R
authors.lastname: Gesztelyi
authors.forename: J
authors.initials: J
authors.lastname: Zsuga
authors.forename: T
authors.initials: T
authors.lastname: Bányász
authors.forename: J
authors.initials: J
authors.lastname: Magyar
authors.forename: P
authors.initials: P
authors.lastname: Szigligeti
authors.forename: L
authors.initials: L
authors.lastname: Kovács
authors.forename: A
authors.initials: A
authors.lastname: Jednákovits
authors.forename: A J
authors.initials: AJ
authors.lastname: Szentmiklósi
authors.forename: P P
authors.initials: PP
authors.lastname: Nánási
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007094:Imides / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: C414244:BRX 005; D002316:Cardiotonic Agents; D007094:Imides; D011725:Pyridines; C108730:bimoclomol; D002118:Calcium