Effects of age on neurotransmission at the cardiac sympathetic neuroeffector junction

The effect of age on the capacity of the right cardiac sympathetic nerve to release norepinephrine (NE) into perfusion effluent (NE overflow) was studied in hearts isolated from male Fischer 344 rats at 6, 12 and 24 months of age. The hearts were perfused through an aortic cannula with Krebs-Ringer solution and the cardiac sympathetic nerve was stimulated electrically with supra-maximal voltage at frequencies of stimulation that produced 20%, 50% or 80% of maximal NE overflow at each age. The content of NE in the perfusion effluent was measured by electro-chemical detection after alumina extraction and high-performance liquid chromatography separation. The NE overflow was significantly lower in hearts of 12- and 24-month-old animals compared to hearts from 6-month-old animals at each frequency of stimulation. In addition the frequency of stimulation necessary to produce 50% or 80% of maximal NE overflow was significantly greater in heart preparations from both 12- and 24-month-old animals compared to preparations from 6-month-old animals. Perfusion with cocaine (10(-6) M) significantly increased the quantity of NE in the effluent after nerve stimulation only in hearts from 12- and 24-month-old animals. Nevertheless, NE overflow remained significantly lower than that observed in hearts of 6-month-old animals. The results suggest that the capacity of the cardiac sympathetic nerve to release NE is diminished in 12- and 24-month-old animals. Furthermore, in these age groups an increase in neuronal uptake appears to reduce further the quantity of NE made available to the heart. These changes seem to occur by middle age and persist to senescence.