Figure 4.

Effect of endogenous NO^⋅ on cardiac SR ⁴⁵Ca uptake under various conditions. Vesicles in the absence of NOS substrates, cofactors, and SOD (A); −SOD + thapsigargin (B) (Tg, a specific inhibitor of Ca²⁺-ATPase); vesicles + SOD (C); + SOD + Tg (D); condition C in the presence of NOS substrates and cofactors for 30 min (E), or for 60 min (F) (30 min at 23°C and 30 min at 37°C); 60-min incubation (same as F) in the presence of the NOS inhibitor 7-NI (10 μM) (G); d-arginine replaced l-arginine in condition F (H). Data represent the mean ± SD from six independent experiments by using 0.6 mg/ml cardiac SR vesicles. The concentration of SOD was 300 units/ml in all reaction mixtures. ⁴⁵Ca uptake is inhibited by endogenously produced NO^⋅. The results suggest that cardiac NOS regulates SR ⁴⁵Ca uptake by directly modifying Ca²⁺-ATPase function through endogenous NO^⋅.