Cardiovascular effects of BRX-005 comparison to bimoclomol

Concentration-dependent effects of BRX-005, the novel heat shock protein co inducer, cardioprotective and vasoprotective agent, on intracellular calciu m transients and contractility were studied in Langendorff-perfused guinea pig hearts loaded with the fluorescent calcium indicator dye Fura-2. BRX-00 5 increased peak left ventricular pressure, the rate of force development a nd relaxation significantly in a concentration-dependent manner. The amplit ude 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 o f BRX-005 had no effect on depolarization, whereas bimoclomol suppressed ac tion potential upstroke markedly. In guinea pig pulmonary artery preparatio ns precontracted with phenylephrine, BRX-005 induced concentration-dependen t relaxation. This effect of BRX-005 was independent of the integrity of en dothelium indicating that vasorelaxant effect of the drug develops directly on vascular smooth muscle, (C) 2000 Elsevier Science Inc. All rights reser ved.