Cardiovascular effects of BRX-005 comparison to bimoclomol.
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.
Körtvély
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A
Department of Physiology, University Medical School of Debrecen, Hungary.
Szigeti
G
G
Gesztelyi
R
R
Zsuga
J
J
Bányász
T
T
Magyar
J
J
Szigligeti
P
P
Kovács
L
L
Jednákovits
A
A
Szentmiklósi
A J
AJ
Nánási
P P
PP
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
C414244:BRX 005; D002316:Cardiotonic Agents; D007094:Imides; D011725:Pyridines; C108730:bimoclomol; D002118:Calcium