The field stimulation induced release of 3H-norepinephrine (NE) from the isolated portal vein and endogenous NE from the isolated caudal artery and perfused mesenteric arterial bed of spontaneously hypertensive rats (SHR) and age-matched normotensive rats (Wistar-Kyoto or Sprague-Dawley) was studied. There was a significantly greater release of NE from all three preparations obtained from 10- to 12-week-old SHR compared to normotensive animals. In addition, there was a greater release of NE from the caudal artery of 5- to 6-week-old SHR compared to controls. No differences were seen in the evoked release of NE from portal vein or caudal artery obtained from renal or DOCA salt hypertensives compared to vessels obtained from sham controls. Neuropeptide Y (NPY) produced a concentration-dependent decrease in the field stimulation induced release of NE from the perfused mesenteric artery. Low concentrations of NPY decreased while higher concentrations potentiated the increase in perfusion pressure. The NPY induced inhibition of evoked NE release was not altered by α1- or α2-adrenoceptor antagonists while the α1-adrenoceptor antagonist, prazosin, prevented the postjunctional response. These results are consistent with there being an alteration of NE release at the vascular neuroeffector junction in SHR which may contribute to the development or maintenance of hypertension. NPY exerts a modulatory role in noradrenergic transmission at the vascular neuroeffector juncti