ENDOTHELIAL INHIBITION OF MYOFILAMENT CALCIUM RESPONSE IN INTACT CARDIAC MYOCYTES

Recent studies suggest that factors released by endothelial cells can modify contraction of isolated cardiac preparations. We compared the e ffects of 1) coronary effluent collected from Langendorff-perfused rat hearts and 2) cultured vascular endothelial cell superfusate on isola ted fura 2-loaded rat ventricular cardiac myocytes. Coronary and cultu red cell effluent produced similar effects. Isotonic contraction ampli tude was reduced by 31.6 +/- 2.6 and 70.2 +/- 9.1%, respectively; myoc yte diastolic length increased by 0.8 +/- 0.2 and 1.5 +/- 0.4 mu m, an d time to 50% relaxation fell by 6.2 +/- 1.8 and 10.1 +/- 2.0% (all P < 0.05; n = 29 and 15 myocytes, respectively). A small fall in the amp litude of the intracellular Ca2+ transient was observed (8.5 +/- 1.5 a nd 10.9 +/- 3.5%, respectively; both P < 0.01), insufficient to accoun t for the reduction in twitch amplitude. In intact; myocytes tetanized in the presence of thapsigargin, the steady-state myofilament respons e to Ca2+ was reduced by coronary and cultured cell effluent. These re sults suggest that both coronary endothelial cells in situ and culture d endothelial cells tonically release a factor(s) that reduces myofila ment Ca2+ response.