Sarcoplasmic reticulum and endothelium independently regulate venous smooth muscle [Ca2+](i) and contraction

In rings of rabbit facial vein (RFV), depletion of sarcoplasmic reticulum ( SR) Ca2+ by caffeine abolished the subsequent isometric contraction to 25 m M K+ physiological salt solution (25K-PSS). However, the associated steady- state increase of smooth muscle intracellular free Ca2+ concentration ([Ca2 +](i)), measured using fura PE3 and cuvette photometry, was not altered. Tr eatment with the specific SR Ca2+ pump inhibitor cyclopiazonic acid (30 mu M) after caffeine-induced SR Ca2+ depletion restored and greatly augmented the 25K-PSS-induced contraction. This suggests that SR Ca2+ depletion leads to a dissociation of K+-induced [Ca2+](i) increase from contraction that w as dependent on Ca2+ pump-mediated SR Ca2+ uptake. Endothelium removal augm ented the 25K-PSS-induced [Ca2+](i) increase after caffeine-induced SR Ca2 depletion. However, this was associated with only a small and transient co ntraction. Exposure of endothelium-denuded RFV to cyclopiazonic acid after caffeine-induced SR Ca2+ depletion further amplified the 25K-PSS-induced [C a2+](i) increase, which was associated with a large and sustained contracti on. However, the latter [Ca2+](i) increase was still higher than in endothe lium-intact RFV. This suggests that the endothelium dampens the [Ca2+](i) r ise associated with K+-induced Ca2+ influx, but independently of Ca2+ pump- mediated SR Ca2+ uptake.