Prejunctional and Postjunctional Effects of Neuropeptide Y at the Noradrenergic Neuroeffector Junction of the Perfused Mesenteric Arterial Bed of the Rat

Abstract

The effect of neuropeptide Y (NPY) on periarterial nerve stimulation-induced release of norepinephrine (NE) and increase in perfusion pressure in the perfused mesenteric arterial bed of the rat was examined. Perfusate effluents were continuously collected and assayed for endogenous NE by high-pressure liquid chromatography (HPLC) coupled to electrochemical detection. Perfusion pressure was continuously monitored by means of a pressure transducer. Periarterial nerve stimulation (8 or 16 Hz, V, 2-ms duration for 30 s) resulted in a readily detectable increase in NE release and perfusion pressure that was atteuated by the prior administration of tetrodotoxin (TTX) (10-5 M) or guanethidine (5 .times. 10-5 M). NPY exerted both prejunctional and postjunctional effects on noradrenergic neurotransmission in this penetration. The peptide produced a concentration-dependent reduction in the release of NE over a concentration range of 10-10-10-7 M. A similar inhibition effect occurred at 8, 10, and 16 Hz. In contrast, low concentrations (10-10 and 10-9 M) decreased the effect of nerve stimulation on perfusion pressure, whereas higher concentrations (10-7 M) produced a marked potentiation. The .alpha.2-adrenoceptor antagonist, yohimbine, did not alter the inhibitory effect of NPY on evoked NE release or the effect on perfusion pressure. Prazosin similarly did not alter the inhibitory effect of NPY on NE release but prevented the increase in perfusion pressure. We conclude that NPY modulates noradrenergic neurotransmission in the msenteric arterial bed by decreasing the evoked release of NE and producing a concentration-dependent biphasic response on vascular smooth muscle. The inhibiton of NE produced by low concentrations of NPY results in a decrease in perfusion pressure whereas high concentrations produce a marked increase in perfusion pressure.