Reduction in sarcoplasmic reticulum Ca2+-ATPase activity contributes to age-related changes in the calcium content and relaxation rate of rabbit aortic smooth muscle.

摘要

OBJECTIVE: Elevated blood pressure is a common effect of aging that results from alterations in the calcium (Ca2+) homeostatic mechanisms in vascular smooth muscle cells. The sarcoplasmic reticulum is a primary subcellular organelle involved in Ca2+ homeostasis in vascular smooth muscle. This study was therefore undertaken to delineate possible age-associated changes that occur in the sarcoplasmic reticulum Ca2+ homeostatic mechanisms. METHODS: Relaxation rates after phenylephrine-induced contractions in aortic smooth muscle from rabbits of increasing age were evaluated in the presence of thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor. In addition, electron probe X-ray microanalysis (EPMA) was used to analyze the total calcium content of the sarcoplasmic reticulum and cytosol in aortic smooth muscle from rabbits of various ages. RESULTS: The relaxation rate of rabbit aorta contracted with phenylephrine declined with age, the decline being progressively reduced when Ca2+ uptake by the sarcoplasmic reticulum was abolished by thapsigargin. EPMA measurements demonstrated an increased cytosolic calcium content and possibly reduced sarcoplasmic reticulum calcium content in arteries from older animals compared with arteries from juvenile animals. CONCLUSIONS: Reuptake of Ca2+ by the sarcoplasmic reticulum is necessary for optimal relaxation of rabbit aorta after a maximal, agonist-induced contraction. The present data suggest that impaired activity of the sarcoplasmic reticulum Ca2+ pump associated with aging may contribute to the increased cytosolic calcium content and elevated resting tone of aortic smooth muscle obtained from older rabbits.