Age-related changes in interstitial norepinephrine. A microdialysis study in spontaneously hypertensive rats

This study was aimed at evaluating the time course of interstitial norepinephrine (NE) concentrations in the white adipose tissue and at assessing NE release after local perfusion with tyramine hydrochloride (TYR) in rats of different ages. Two groups of eight spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats, aged 14 to 16 weeks, were studied. The same animals were reexamined at the age of 52 to 54 weeks. A soft microdialysis probe was implanted subcutaneously in the parascapular region and was perfused with Ringer solution (flow rate: 2.0 microL/min). After an equilibration period, NE levels were monitored for 120 min, following which, TYR (0.1 nmol/min) was perfused for 90 min. Dialysates from each 30 min collection period were analyzed by HPLC using electrochemical detection. At 14 to 16 weeks, SHR showed higher NE concentrations in dialysates as compared to WKY (1124.0 pg/mL v 541.4 pg/mL; P < .001) and a blunted response to TYR challenge. The net output, estimated by subtracting basal values, was 86.0 pg NE/h in SHR as compared to 212.5 pg NE/ h in WKY (P = .005). Differences in basal NE levels persisted in the same aged groups (P < .001) as well as a blunted response to TYR. The net NE output was still lower in SHR as compared to WKY (320.4 pg NE/h v 414.7 pg NE/h in WKY; P = .023). Basal levels of NE in SHR could be accounted for by either a higher amount of the neurotransmitter stored into and released from vescicles or by an increased firing rate of the sympathetic fibers. Since TYR is known to deplete axoplasmic but not vesicular NE available for neurotransmission, the response of SHR to TYR challenge is consistent with an increased turnover rate of NE. Aging was associated with an increased response to TYR in both strains, thus suggesting an age-dependent decline in turnover rates or changes in NE reuptake mechanisms.