Effects of chloroacetaldehyde in 2-chloroethanol-induced cardiotoxicity.
Cardiovascular effects have often been found in 2-chloroethanol (2-CE) intoxicated patients, but the 2-CE elicits cardiovascular toxicity mechanism is not clear. Recently, we have found that chloroacetaldehyde (CAA) accumulation in 2-CE-intoxicated rat's blood and play an important role in 2-CE intoxication. In this study, we used an isolated rat atrium model to examine the cardiotoxicity of 2-CE and CAA. Results indicated that 2-CE did not cause tension arrest in isolated rat right atria, but CAA did. 2-CE caused tension inhibition in the isolated rat left atria. In addition, CAA caused significant tension inhibition and contracture in the isolated rat left atria. Nifedipine, an L-type calcium channel blocker, decreased CAA-induced tension inhibition and contracture. Meanwhile, atrial nNOS and calmodulin (CaM) had significantly greater expression in the 2-CE group and the CAA group than control group. Nifedipine could decrease CAA-induced nNOS and CaM expression. 2-CE-induced cardiovascular toxicity might be due to its metabolite CAA. CAA-induced cardiovascular toxicity might be mediated by calcium channel and nifedipine protected against nNOS-triggered cardiovascular effects.
Division of Molecular Genomics and Medicine, National Health Research Institutes, Zhunan Town, Miaoli Country 350, Taiwan.
Yng-Tay
YT
Chen
Ching-I
CI
Hsu
Dong-Zong
DZ
Hung
Isao
I
Matsuura
Jiunn-Wang
JW
Liao
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism; D054715:Cardiotoxins / Q000633:toxicity*; D005023:Ethylene Chlorohydrin / Q000633:toxicity*; D006325:Heart Atria / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009206:Myocardium; D009543:Nifedipine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002147:Calmodulin; D054715:Cardiotoxins; D005023:Ethylene Chlorohydrin; C004656:chloroacetaldehyde; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D000079:Acetaldehyde; D009543:Nifedipine