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Experiments have been conducted to evaluate the effect of neuropeptide Y (NPY) administered at three distinct levels of the nervous system: 1) the posterior hypothalamic nucleus, 2) the spinal cord, and 3) the vascular noradrenergic neuroeffector junction. It was observed that NPY produced varying cardiovascular effects at these three distinct sites of the nervous system. Microinjections into the posterior hypothalamic nucleus resulted in an increase in blood pressure, which was reduced by prior microinjection of a muscarinic or H1-histamine antagonist but not an H2-histamine antagonist. In addition to the involvement of histaminergic and cholinergic pathways, the pressor effect of NPY appears to result from an increase in sympathetic outflow. NPY was also seen to decrease the potassium-induced release of norepinephrine (NE) from slices obtained from the posterior hypothalamic nucleus. In contrast to what was observed in the hypothalamus, the intrathecal injection of NPY at a level of T4 or T10 in anesthetized or T10 in unanesthetized rats resulted in a depressor effect as well as a decrease in heart rate. Both an alpha 2- and beta-adrenoceptor antagonist reduced the NPY effect. The depressor effect of intrathecal NPY was attenuated in rats pretreated with reserpine as well as in Spontaneously Hypertensive rats (SHR). These data suggest that the effects of NPY are closely associated with sympathetic preganglionic neurons in the spinal cord. At the vascular noradrenergic neuroeffector junction, NPY decreased the nerve stimulation-induced release of NE while potentiating the contractile response. Moreover, NPY potentiated the increase in perfusion pressure of the perfused mesenteric arterial bed in response to angiotensin, vasopressin, or phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

It was observed that there was a significantly greater field-stimulation induced release of norepinephrine from the portal vein and caudal artery obtained from 28 week old SHR compared to WKY. The greater field-stimulation induced release of norepinephrine observed in the blood vessels of the SHR compared to WKY was not seen in DOCA-salt and one kidney-one clip hypertensive animals with similar elevations of systolic blood pressure. It was also observed that there was an attenuation of the effect of the prejunctional alpha 2-adrenoceptor antagonist, yohimbine to enhance the field-stimulation induced release of norepinephrine from blood vessels of the 28 week old SHR. There was no attenuation of the yohimbine effect in the other two models of hypertension. It is concluded that there is an alteration in the release of norepinephrine from blood vessels of SHR, resulting in a greater evoked release of the transmitter. A decrease in the functional activity of prejunctional alpha 2-adrenoceptor may contribute to the enhanced release of norepinephrine from the blood vessels of the SHR.

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 junction.

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