In vivo and in vitro acute cardiovascular effects of bimoclomol

Effects of bimoclomol, the novel heat shock protein (HSP) coinducer, was st udied in various mammalian cardiac and rabbit aortic preparations. Bimoclom ol decreased the ST-segment elevation induced by coronary occlusion in anes thetized dogs (56% and 80% reduction with 1 and 5 mg/kg, respectively). In isolated working rat hearts, bimoclomol increased coronary now (CF), decrea sed the reduction of cardiac output (CO) and left ventricular developed pre ssure (LVDP) developing after coronary occlusion, and prevented ventricular fibrillation (VF) during reperfusion. In rabbit aortic preparations, preco ntracted with phenylephrine, bimoclomol induced relaxation (EC50=214 muM). Bimoclomol produced partial relaxation against 20 mM KCl, however, bimoclom ol failed to relax preparations precontracted with serotonin, PGF(2) or ang iotensin II. All these effects were evident within a few minutes after appl ication of bimoclomol. A rapid bimoclomol-induced compartmental translocati on of the already preformed HSPs may explain the protective action of the c ompound. (C) 2001 Elsevier Science Inc. All rights reserved.