Preservation of vascular contraction during ageing: dual effect on calcium handling and sensitization

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Abstract
The present study was aimed to characterize the effects of ageing on vascular contraction by noradrenaline in rat isolated arteries. The existence of vascular bed heterogeneity was investigated in endothelium‐denuded conductance (aorta) and resistance (small mesenteric artery, SMA) arteries, with respect to Ca2+handling, Ca2+sensitization or Ca2+‐independent mechanisms. In both arteries, contractions to noradrenaline were not different between adult and aged rats. In Ca2+‐ free medium, noradrenaline elicited a transient increase in tension that was reduced by the Ca2+mobilizing agents, ryanodine and thapsigargin, in arteries from adult rats. A loss of the thapsigargin‐ but not the ryanodine‐sensitive component of noradrenaline‐induced contraction was observed in the two arteries from aged rats. After depletion of Ca2+stores with noradrenaline, addition of exogenous CaCl2produced a sustained contraction that was decreased to the same extent by the protein kinase C inhibitor, GF 109203X and the tyrosine kinase inhibitor, tyrphostin A‐23, in arteries from adult and aged rats. The Rho‐associated protein kinase inhibitor, Y‐27632, caused identical relaxation of noradrenaline pre‐contracted arteries from both age groups. Basal intracellular calcium ([Ca2+]i) was higher in SMA from aged than from adult rats. In addition, the noradrenaline [Ca2+]i‐force relationship was significantly shifted to the right in the SMA from aged rats. Altogether, these data indicate that responsiveness to noradrenaline is preserved both in conductance and resistance arteries with ageing. The latter results from the association of increased basal [Ca2+]i, changes in Ca2+handling at the level of thapsigargin‐sensitive sarcoplasmic reticulum Ca2+‐ATPases and decreased myofilament sensitivity to Ca2+. British Journal of Pharmacology(2003)138, 745–750. doi:10.1038/sj.bjp.0705104