Effect of age on prejunctional modulation of norepinephrine release

The effect of age on prejunctional modulation of norepinephrine release was studied in tail arteries isolated from Fischer-344 rats, age 6 to 27 months. Tail arteries were perfused in vitro, and norepinephrine released during adrenergic nerve stimulation was collected and analyzed by high-pressure liquid chromatography with electrochemical detection. There was no progressive change with age in norepinephrine content in the tail artery, although content at 6 months was significantly less than 12 months. The most significant finding was a decline with age in the effect of the alpha-2 adrenergic antagonist yohimbine to increase norepinephrine release, suggesting an age- related fall in the effectiveness of prejunctional alpha-2 adrenoceptor activation. In the absence of drugs there was an age-related increase in fractional norepinephrine release, and an age-related increase in the effect of deoxycorticosterone and cocaine was also seen. The increased effect of deoxycorticosterone and cocaine appears to be related to increased norepinephrine levels in the junctional cleft as opposed to an age-related increase in the activity of catecholamine metabolism and uptake. These results suggest that the age-related increase in fractional norepinephrine release may be due, in part, to a decline in negative feedback mediated by prejunctional alpha-2 adrenergic receptors.