Modulation of submucosal arteriolar tone by neuropeptide Y Y2 receptors in the guinea-pig small intestine

Objectives: the aims of this study were to determine if the nerves, both intrinsic and extrinsic, supplying intestinal blood vessels were subject to modulation by a neuropeptide Y-2 receptor agonist, N-acetyl[Leu(28), Leu(31)] NPY(24-36). Methods: effects of Y-2 receptor agonist were examined on (i) responses to acetylcholine (ACh) and intrinsic vasodilator nerve stimulation in normal arterioles and (ii) amplitudes of arteriolar constrictions and smooth muscle membrane potential changes in response to extrinsic perivascular nerve stimulation in both normal and capsaicin-treated arterioles. Results: (i) neuropeptide Y-2 receptor agonist had no significant effect on the relaxing action of exogenous application of ACh but significantly reduced the relaxing action of vasodilator nerve stimulation in arterioles of the isolated submucosa of the guinea-pig small intestine, which were pre-constricted with the thromboxane analogue U46619, (ii) The Y-2 agonist significantly decreased the amplitude of excitatory junction potentials (EJPs) evoked by perivascular nerve stimulation in normal arterioles and in arterioles treated with the sensory neurotoxin, capsaicin. On the other hand, the Y-2 agonist failed to alter the amplitude of the constrictions obtained by perivascular nerve stimulation in normal arterioles but significantly attenuated the amplitude of constrictions in arterioles treated with capsaicin. Conclusions: it is concluded that NPY can modulate release of transmitter from extrinsic sympathetic as well as the intrinsic submucosal vasodilator nerves via prejunctional Y-2 receptors. (C) 1998 Elsevier Science B.V. All rights reserved.