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Alterations by age of calcium handling in rat resistance arteries

Abstract:

This study investigated the alterations by age of Ca2+ handling in rat small mesenteric arteries. The contractile responses to phenylephrine and caffeine in small mesenteric arteries from young and old rats were studied in Ca2+-containing and Ca2+-free medium. In Ca2+-containing medium the contraction to phenylephrine (100 μM) but not to caffeine (10 mM) was greater in old than in young rats. Concentration-response curve to phenylephrine was affected to the same extent by nifedipine (1 μM) in both age groups, whereas ryanodine (20 μM) decreased the maximal response to phenylephrine only in young rats. These results suggest the participation of intracellular Ca2+ handling on the observed differences by aging. In Ca2+-free medium, phenylephrine (10 μM) but not caffeine (10 mM) induced a greater contraction in old than in young animals, corroborating the results obtained in Ca2+-containing solution. The greater response to phenylephrine observed in old rats cannot be explained by an increase in the inositol 1,4,5-trisphosphate (IP3) formation because the accumulation of inositol phosphates by phenylephrine was not affected by aging. Results obtained in Ca2+-free medium using caffeine after phenylephrine or vice versa suggest a common intracellular Ca2+ pool. Pretreatment with ryanodine in Ca2+-free medium almost abolished contractile response to phenylephrine and caffeine in young rats but only partially decreased them in old animals, suggesting an impairment in the Ca2+-induced Ca2+ release (CICR) mechanism leading to an increase in the stored Ca2+ content. The greater amount of stored Ca2+ could explain the higher contractile response to phenylephrine observed in aged rats. As a consequence of all these changes due to aging, an imbalance between the two Ca2+ release mechanisms from sarcoplasmic reticulum was observed with a major role of Ca2+ induced release by IP3 at the expense of an impairment of CICR mechanism. This observation will also help explain the results obtained in the presence of extracellular Ca2+, where phenylephrine induced a greater maximum response in old animals in spite of a decrease in the midrange sensitivity to this agonist.