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 sub stances in the superfusing blood may thus participate in the control o f 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 d uration was slightly increased (time from stimulus to half isometric r elaxation, +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 effe ct. Interestingly, the positive inotropic effect was completely blocke d by selectively damaging endocardial endothelium (Triton X-100, 0.5%, 1-s immersion, n=7) before ROS generation and by preincubating the mu scles with the endothelin-h receptor antagonist BQ 123 (n=11). Preincu bation with N-G-nitro-L-arginine methyl ester and indomethacin (n=5) o r with atenolol (n=6) did not influence the inotropic effect. Confocal scanning laser microscopic observations of muscles stained with viabi lity tracers (n=9) revealed that significantly more but not all endoca rdial endothelial cells were damaged in electrolysis-treated muscles t han in control muscles (42+/-5% versus 14+/-4%, P<.05). Accordingly, b rief exposure of isolated cardiac muscle to electrolysis-generated ROS damaged the endocardial surface in part and increased contractile per formance by stimulating endothelin release from endocardial endotheliu m. Hence, ROS-induced endothelin release from endocardial endothelium may be involved in normal and/or disturbed regulation of cardiac funct ion.