Rat tail artery norepinephrine release: age and effect of mitochondrial blockade

An age-related increase in stimulation-evoked fractional norepinephrine release has been demonstrated in tail artery of Fischer-344 rats from 6 to 20 months of age. Previous studies have ruled out alterations in function of uptake mechanisms, metabolism, or feedback via prejunctional alpha-2 adrenoceptors, suggesting that an age-related decline in calcium homeostasis may be responsible. To test this possibility, stimulation-evoked fractional norepinephrine release from perivascular adrenergic nerves of rat tail arteries in the presence of a blocker of mitochondrial calcium uptake, dinitrophenol (100 microM), was measured using HPLC with electrochemical detection. When the mitochondrial proton gradient was dissipated by dinitrophenol, tail arteries from 20-month-old animals showed a marked increase in stimulation-evoked norepinephrine release whereas arteries from 6-month-old animals were not affected. One hypothesis is that the inhibition of mitochondrial calcium uptake in the adrenergic nerves from older animals resulted in an elevated intracellular calcium level. In agreement with this idea, when extracellular calcium was raised from 1.6 to 5 mM, stimulation-evoked norepinephrine release was increased in the 6-month tail arteries in the presence of dinitrophenol. These data suggest that there may be a decline in calcium regulation in older nerves leading to increased norepinephrine release with advancing age.