LONG-TERM GUANETHIDINE SYMPATHECTOMY SUPPRESSES FLOW-INDUCED RELEASE OF ATP AND ENDOTHELIN FROM ENDOTHELIAL-CELLS ISOLATED FROM ADULT-RAT AORTA

Chronic rather than acute changes in the autonomic innervation of the vasculature are a feature of ageing and several cardiovascular disorde rs. To investigate the long-term influence of perivascular innervation on the vascular endothelium, the release of vasoactive substances whi ch have been localised in endothelial cells, namely ATP, endothelin, s ubstance P and vasopressin, was monitored from cells isolated from adu lt rat thoracic aorta following neonatal guanethidine sympathectomy. T he endothelial cells were initially perfused at 0.5 ml/min and exposed to two periods of increased flow at 3.0 ml/min. Cells isolated from c ontrol rats released significantly more ATP on both occasions of switc hing from the lower to higher flow rate and significantly more endothe lin on the second exposure to the higher flow rate. In contrast, endot helial cells isolated from sympathectomised rats showed no increased r elease of either ATP or endothelin with increased flow, although the r elease of endothelin at the initial flow rate of 0.5 ml/min was higher than in the controls. Substance P and vasopressin levels in the perfu sate were the same in controls and after sympathectomy. In summary, lo ng-term sympathectomy suppresses increased flow-induced release of sel ected vasoactive substances from the endothelium, thus shear-stress-in duced changes in local blood flow may be impaired when there are chron ic disturbances in the autonomic innervation.