Neuropeptide Y potentiates a, b‐methylene ATP‐evoked contractions via NPY receptors 1 and 2 in mouse mesenteric arteries

Resumen

Background and Purpose: Neuropeptide Y (NPY) is a neuromodulator released along with norepinephrine (NE) and ATP at sympathetic varicosities that innervate small arteries. NPY is known to positively enhance contractile responses to NE, but mechanisms underlying NPY modulation of purinergic receptors elicited by ATP are less clear. Here, we investigate the influence of NPY on purinergic contractions in mouse resistance‐sized arteries. Experimental Approach: Adult male C57BL/6 mice (20–30 g) were used following the requirements of the Animals (Scientific Procedures) Act 1986/ASPA Amendment Regulations 2012. First‐order mesenteric arteries (<200 μm) were dissected, cut into 2‐mm rings, and mounted in a Mulvany myograph. Drugs were directly added to the chamber, while vessel force was monitored. Data are expressed as mean ± SEM, and n represents the number of animals. Analysis was performed using ANOVA or Kruskal–Wallis test followed by a Student–Newman–Keuls t test, post hoc Tukey honestly significant difference test, or Mann–Whitney U‐test where appropriate. Comparison between segments from the same animals was assessed by a pairedt test or a Wilcoxon signed‐rank test. Key Results: The purinergic agonist α,β‐methylene ATP (α,β‐meATP) evoked concentration‐dependent contractions (EC50 226 ± 34 nM; N = 5). α,β‐meATP‐evoked responses were insensitive to L‐typeCa2+ channel blockade (1–100 nM nifedipine: P < .05; N = 5) but abolished by suramin (IC50 28 ± 7 μM; N = 5) and the selective P2X1 receptor antagonist NF449 (IC50 466 ± 59 nM; N = 5). Nifedipine abolished contractions evoked by high K+ solution (60 mM K+). Preincubation with NPY (10–30 nM) potentiated the response to submaximal concentrations of α,β‐meATP (100 nM) up to 154% over vehicle control (P > .05; N = 9). The ability of NPY to potentiate α,β‐ meATP‐evoked contractions was partially reduced by selective NPY R1 antagonism (BIBO3304, 10 nM; 40%; P < .05; N = 6) or NPY R2antagonism (BIIE0246, 100 nM; 9%; P < .05; N = 5). However, the potentiating effect of NPY was abolished when BIBO3304 and BIIE0246 were applied in combination.