Age-related decrease in the effect of parathyroid hormone-related protein on cytosolic free calcium level and tension in rat aortic smooth muscle

Abstract

Age-related changes in the effect of parathyroid hormone-related protein (PTHrP) on the cytosolic free calcium level ([Ca2+]i) and on the tension in rat aortic smooth muscle were investigated. The possible involvement of cAMP, a second messenger of PTHrP, in such changes was also 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 measured. Simultaneously, the tension of the preparations was measured. PTHrP-(1-34) and dibutyryl cAMP produced concentration-dependent decreases in the tension and in R340/380 in aortas precontracted with phenylephrine (10(-7) M). These effects were significantly lower in the aortas 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-months old rats. PTHrP-(1-34) concentration-dependently increased cAMP production 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 production stimulated by PTHrP and the reduced effects of cAMP with aging might contribute to the age-related changes in the decreases in tension and [Ca2+]i in response to PTHrP in the rat aorta.

Biochemical and Molecular Aspects of Vascular Adrenergic Regulation of Blood Pressure in the Elderly

“…One interpretation of this result is that with advancing age, isoproterenol-mediated signaling pathways involve an increased role for K+ channels. Further support that the aging change in β -AR signaling is vascular smooth muscle-, rather than endothelium-dependent is that other agents that initiate vasorelaxation through vascular smooth muscle localized G protein-coupled receptors (adenosine, parathyroid hormone) also show impaired vasorelaxation with age [ 105 , 106 ]. Therefore, the age-related change is likely due to a factor common to all vascular smooth muscle-localized G protein-coupled receptors, such as GRK (see above discussion), while a nonage-related endothelial dependent component contributes to β -AR-stimulated vasorelaxation in general.…”

Cell-cell communication predicts aging, senescence and death: an integrated, predictive evolutionary approach

“…In bone, there are several studies showing decline in the response of bone to both endogenous (34; 35) and a waning response of bone to exogenous PTHrP (36; 37). Moreover, there is evidence of loss of bioactivity of PTHrP in regulating calcium activity in rat aortic smooth muscle (38).…”