REDUCTION IN SARCOPLASMIC-RETICULUM CA2-ATPASE ACTIVITY CONTRIBUTES TO AGE-RELATED-CHANGES IN THE CALCIUM CONTENT AND RELAXATION RATE OF RABBIT AORTIC SMOOTH-MUSCLE()

Objective Elevated blood pressure is a common effect of aging that res ults 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+ homeo static mechanisms. Methods Relaxation rates after phenylephrine-induce d contractions in aortic smooth muscle from rabbits of increasing age were evaluated in the presence of thapsigargin, a sarcoplasmic reticul um Ca2+-ATPase inhibitor, In addition, electron probe X-ray microanaly sis (EPMA) was used to analyze the total calcium content of the sarco- plasmic reticulum and cytosol in aortic smooth muscle from rabbits of various ages. Results The relaxation rate of rabbit aorta contracted w ith phenylephrine declined with age, the decline being progressively r educed when Ca2+ uptake by the sarcoplasmic reticulum was abolished by thapsigargin. EPMA measurements demonstrated an increased cytosolic c alcium content and possibly reduced sarcoplasmic reticulum calcium con tent in arteries from older animals compared with arteries from juveni le 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 ac tivity of the sarcoplasmic reticulum Ca2+ pump associated with aging m ay contribute to the increased cytosolic calcium content and elevated resting tone of aortic smooth muscle obtained from older rabbits.