Endothelin-mediated positive inotropic effect induced by reactive oxygen species in isolated cardiac muscle.
Cardiac endothelium, both coronary and endocardial, produces a number of inotropic molecules. Changes in cardiac endothelial function by substances in the superfusing blood may thus participate in the control of muscle-pump performance of the heart. Reactive oxygen species (ROS) have been implicated in normal and pathological vascular physiology by influencing vascular endothelial function. Therefore, we examined the influence of ROS on endocardial endothelial modulation of myocardial performance. Right ventricular cat papillary muscles were briefly (15 s) exposed to electrolysis-generated ROS. Peak total isometric twitch tension and peak rate of tension development increased by 7.8 +/- 0.7% (P < .05) and 9.7 +/- 1.5% (P < .05), respectively (n = 12). Isometric twitch duration was slightly increased (time from stimulus to half isometric relaxation, +2.7 +/- 0.6%; P < .05). ROS scavengers such as ascorbic acid (n = 6), superoxide dismutase and catalase (n = 8), or catalase alone (n = 6), but not superoxide dismutase alone (n = 6), blocked the inotropic effect. Interestingly, the positive inotropic effect was completely blocked by selectively damaging endocardial endothelium (Triton X-100, 0.5%, 1-s immersion, n = 7) before ROS generation and by preincubating the muscles with the endothelin-A receptor antagonist BQ 123 (n = 11). Preincubation with NG-nitro-L-arginine methyl ester and indomethacin (n = 5) or with atenolol (n = 6) did not influence the inotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
De Keulenaer
G W
GW
Department of Physiology and Medicine, University of Antwerp, Belgium.
Andries
L J
LJ
Sys
S U
SU
Brutsaert
D L
DL
D000818:Animals; D002415:Cats; D002470:Cell Survival / Q000187:drug effects; D016232:Endothelins / Q000096:biosynthesis* / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism*; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000494:pharmacology*
D016232:Endothelins; D017382:Reactive Oxygen Species