Effects of the reactive oxygen species hypochlorous acid and hydrogen peroxide on force production and calcium sensitivity of rat cardiac myofilaments.
Neutrophil activation occurs after myocardial infarction/ischaemia. They produce the reactive oxygen species (ROS) hypochlorous acid (HOCl) and hydrogen peroxide (H2O2) which could contribute to contractile dysfunction upon reperfusion. The myofilaments of 'skinned' rat cardiac muscle were exposed to ROS in various states of activation. Isometric force was measured at controlled degrees of activation. A single application of 10 microM HOCl for 1 min increased log [Ca2+] for half-maximal activation (log K1/2) from 5.23 to 5.32, initial maximum Ca-activated force (FCa, max) was reduced by 18.8 +/- 5.8% and resting tension increased to 15.4 +/- 8.0% of FCa, max. At 50 microM, a 1-min exposure to HOCl produced a greater increase in Ca-sensitivity (log K1/2 increased from 5.23 to 5.47), a greater reduction in FCa, max (falling by 42.3 +/- 23.2%) and a greater increase in resting tension (to 25 +/- 10.7% of FCa, max). The nature of the resting tension rise was examined by reducing pH before and during exposure to HOCl; the results are consistent with 'rigor-like' cross-bridges being involved. H2O2 was without effect on the myofilaments at physiologically relevant (< 10 microM) concentrations. These results suggest that ROS associated with inflammation could contribute to post-ischaemic myocardial dysfunction.
Institute of Physiology, Glasgow University, Scotland, UK.
N G
NG
MacFarlane
D J
DJ
Miller
D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D010100:Oxygen; D002118:Calcium