AGE-RELATED DECREASE IN THE EFFECT OF PARATHYROID HORMONE-RELATED PROTEIN ON CYTOSOLIC-FREE CALCIUM LEVEL AND TENSION IN RAT AORTIC SMOOTH-MUSCLE

Age-related changes in the effect of parathyroid hormone-related prote in (PTHrP) on the cytosolic free calcium level ([Ca2+](i)) and on the tension in rat aortic smooth muscle were investigated. The possible in volvement of cAMP, a second messenger of PTHrP, in such changes was al so investigated. Spiral aortic strip preparations without endothelium from 8-weeks, 6-months, and 24-months old rats were treated with fura 2/AM, and the fluorescence ratio R340/380, an index of [Ca2+](i) was m easured. Simultaneously, the tension of the preparations was measured. PTHrP-(1-34) and dibutyryl cAMP produced concentration-dependent decr eases in the tension and in R340/380 in aortas precontracted with phen ylephrine (10(-7) M). These effects were significantly lower in the ao rtas of 24-months old rats than in the vessels of 8-weeks and 6-months old rats. The effects were similar in the aortas of 8-weeks and 6-mon ths old rats. PTHrP-(1-34) concentration-dependently increased cAMP pr oduction in vascular smooth muscle cells (VSMCs) from 8-weeks old rats . However, the increase in cAMP production was significantly lower in cultured VSMCs from 6-months and 24-months old rats than in cells from 8-weeks old rats. These results suggest that the reduced cAMP product ion stimulated by PTHrP and the reduced effects of cAMP with aging mig ht contribute to the age-related changes in the decreases in tension a nd [Ca2+](i) in response to PTHrP in the rat aorta.