Cerebral artery sarcoplasmic reticulum Ca 2ϩ stores and contractility: changes with development. Am J Physiol Regulatory Integrative Comp Physiol 279: R860-R873, 2000.-To test the hypothesis that sarcoplasmic reticulum (SR) Ca 2ϩ stores play a key role in norepinephrine (NE)-induced contraction of fetal and adult cerebral arteries and that Ca 2ϩ stores change with development, we performed the following study. In main branch middle cerebral arteries (MCA) from near-term fetal (ϳ140 days) and

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... pregnant adult sheep, we measured NE-induced contraction and intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) in the absence and presence of different blockers. In adult MCA, after thapsigargin (10 Ϫ6 M), the NE-induced responses of tension and [Ca 2ϩ ] i were 37 Ϯ 5 and 47 Ϯ 7%, respectively, of control values (P Ͻ 0.01 for each). In the fetal artery, in contrast, this treatment resulted in no significant changes from control. When this was repeated in the absence of extracellular Ca 2ϩ , adult MCA increases in tension and [Ca 2ϩ ] i were 32 Ϯ 5 and 13 Ϯ 3%, respectively, of control. Fetal cerebral arteries, however, showed essentially no response. Ryanodine (RYN, 3 ϫ 10 Ϫ6 to 10 Ϫ5 M) resulted in increases in tension and [Ca 2ϩ ] i in both fetal and adult MCA similar to that seen with NE. For both adult and fetal MCA, the increased tension and [Ca 2ϩ ] i responses to RYN were essentially eliminated in the presence of zero extracellular Ca 2ϩ . These findings provide evidence that in fetal MCA, in contrast to those in the adult, SR Ca 2ϩ stores are of less importance in NE-induced contraction, with such contraction being almost wholly dependent on Ca 2ϩ flux via plasma membrane L-type Ca 2ϩ channels. In addition, they suggest that in both adult and fetal MCA, the RYN receptor is coupled to the plasma membrane Ca 2ϩ -activated K ϩ channel and/or L-type Ca 2ϩ channel. cerebrovascular circulation; vascular smooth muscle; sympathetic nervous system; norepinephrine; intracellular calcium; thapsigargin; cyclopiazonic acid; ryanodine; L-type calcium channel; fetus; adult CONTRACTION OF VASCULAR SMOOTH muscle is dependent on an increase in cytosolic free Ca 2ϩ concentration ([Ca 2ϩ ] i ) as a result of rapid Ca 2ϩ release from intracellular stores, chiefly sarcoplasmic reticulum (SR), and from Ca 2ϩ flux via plasma membrane Ca 2ϩ channels. Recently we reported that fetal ovine cerebral arteries, in contrast to those in the adult, are exquis-Address for reprint requests and other correspondence: L. D.