Dependence of hypotensive effect of neuropeptide-Y 18–36 fragment on intact vagus nerves

Abstract

Effects of neuropeptide Y (NPY 2.35–4.7 nmol) and the fragment NPY 18–36 (3.6–36 nmol) were studied in anaesthetized rats before and after vagotomy for actions on blood pressure (a postjunctional action) and on the change in pulse interval evoked by stimulation of the cut, peripheral vagus nerve (a prejunctional action). In intact rats NPY increased blood pressure. Low doses of NPY 18–36 (2.3–4.7 nmol) also increased blood pressure slightly but higher doses only transiently increased blood pressure and this was followed by a prolonged decrease in blood pressure. In vagotomised rats NPY increased blood pressure and attenuated cardiac vagal action. In higher doses the presynaptic effect of NPY 18–36 was more marked than its pressor action. NPY 18–36 (3.6–36 nmol) also increased blood pressure and attenuated cardiac vagal action. Thus, we conclude that the hypotensive action of NPY 18–36 depends on the intact vagus nerves: in the vagotomised rat NPY 18–36 has similar biological activity to NPY, but with reduced potency. To examine further the mechanism of hypotensive action of NPY 18–36 arterial rings from the central artery of the rabbit ear were also tested for direct actions of the peptides. This preparation is also suitable for testing any potentiation of contraction evoked by injection of noradrenaline. Neither NPY nor NPY 18–36 caused direct constrictor action in concentrations up to 10 μM. NPY 18–36 had no relaxing effect on constricted arterial rings. Both NPY (5 nM) and NPY 18–36 (5 nM-2.5 μM) significantly potentiated the constrictor effect of noradrenaline, supporting the conclusion from the in vivo studies that NPY 18–36 has no direct relaxing action on arterioles.