Mechanisms underlying pre‐ and postjunctional effects of neuropeptide Y in sympathetic vascular control

Abstract

The effects of porcine neuropeptide Y (NPY) regarding sympathetic vascular control were studied in vitro on isolated rat blood vessels. The 10 ^-9 M NPY enhanced (about two-fold) the contractile responses to transmural nerve stimulation (TNS), noradrenaline (NA) and adrenaline (about two-fold) in the femoral artery. Higher concentrations of NPY (> 10^-8 M) caused an adrenoceptor-resistant contraction per se. The TNS-evoked [³H]NA efflux was significantly reduced by NPY in a concentration-dependent manner (threshold 10 ^-9 M). The calcium antagonist, nifedipine, abolished the contractile effects of NPY and the NPY-induced enhancement of NA contractions but did not influence the prejunctional inhibition of [³H]NA release. Receptor-binding studies showed that the ratio of alpha₁- to alpha₂-adrenoceptors in the femoral artery was 30:1. The NPY did not cause any detectable change in the number of alpha₁- or alpha₂-adrenoceptor binding sites or in the affinity of alpha₂-binding sites, as revealed by prazosin- and clonidine-binding, respectively. The NPY also inhibited the TNS-evoked [³H]NA release (by 42–86%) in the superior mesenteric and basilar arteries and in femoral and portal veins. The NPY still depressed TNS-evoked [³H]NA secretion from the portal vein in the presence of phentolamine. The NPY caused a clear-cut contraction in the basilar artery, increased the contractile force of spontaneous contractions in the portal vein, while only weak responses were observed in the superior mesenteric artery and femoral vein. The NA-induced contraction was markedly enhanced by NPY in the superior mesenteric artery, only slightly enhanced in the portal vein and uninfluenced in the femoral vein. In conclusion, in all blood vessels tested, NPY depresses the TNS-evoked [³H]NA secretion via a nifedipine-resistant action. Furthermore, NPY exerts a variable, Ca²⁺-dependent vasoconstrictor effect and enhancement of NA and TNS contractions.