In vivo and in vitro acute cardiovascular effects of bimoclomol.
Effects of bimoclomol, the novel heat shock protein (HSP) coinducer, was studied in various mammalian cardiac and rabbit aortic preparations. Bimoclomol decreased the ST-segment elevation induced by coronary occlusion in anesthetized dogs (56% and 80% reduction with 1 and 5 mg/kg, respectively). In isolated working rat hearts, bimoclomol increased coronary flow (CF), decreased the reduction of cardiac output (CO) and left ventricular developed pressure (LVDP) developing after coronary occlusion, and prevented ventricular fibrillation (VF) during reperfusion. In rabbit aortic preparations, precontracted with phenylephrine, bimoclomol induced relaxation (EC(50)=214 microM). Bimoclomol produced partial relaxation against 20 mM KCl, however, bimoclomol failed to relax preparations precontracted with serotonin, PGF(2) or angiotensin II. All these effects were evident within a few minutes after application of bimoclomol. A rapid bimoclomol-induced compartmental translocation of the already preformed HSPs may explain the protective action of the compound.
Jednákovits
A
A
Biorex Research and Development Co., PO Box 348, H-8201, Veszprém-Szabadságpuszta, Hungary.
Ferdinándy
P
P
Jaszlits
L
L
Bányász
T
T
Magyar
J
J
Szigligeti
P
P
Körtvély
A
A
Szentmiklósi
J A
JA
Nánási
P P
PP
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003327:Coronary Disease / Q000150:complications; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D007094:Imides / Q000494:pharmacology; D007511:Ischemia / Q000150:complications; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
D007094:Imides; D011725:Pyridines; C108730:bimoclomol