Impaired Norepinephrine Reuptake in Skeletal Muscle But not in Adipose Tissue After the Development of Hypertension in Rats: an in Vivo Microdialysis Study

Abstract

P50 Presynaptic reuptake of norepinephrine (NE) represents the main mechanism to end its effects, once released from sympathetic nerves. This study evaluated the effect of locally administered neuronal uptake inhibitor (desipramine, 10 pmol/min through microdialysis probes) on interstitial NE concentration in the skeletal muscle and subcutaneous adipose tissue from awake and freely moving Wistar-Kyoto (WKY)and spontaneously hypertensive rats (SHR) before and after the development of arterial hypertension. Systolic arterial pressure and plasma NE levels in SHR were similar to WKY at 5 weeks of age, but significantly increased at the age of 16 weeks. Basal interstitial NE was increased in both tissues of young and old SHR as compared to age-matched WKY. Desipramine perfusion induced a higher rise of interstitial NE dialysate from skeletal muscle and adipose tissue of SHR than WKY with a difference in the skeletal muscle between young and old SHR (see graphic). These results indicates an increased interstitial NE turnover in pre-hypertensive SHR, not shown by plasma NE level. Once hypertension is established, NE turnover is always increased in SHR as compared to WKY in both tissues. In addition in the skeletal muscle, where sympathetic efferences are baroreflex-dependent, old SHRs show a reduced interstitial NE reuptake contributing to a higher availability of interstitial NE for postsynaptic vascular effects.