Department of Anatomy, MTA-PTE PACAP Research Group, Medical School, University of Pecs, Pecs, Hungary.
Department of Physiology and Immunology, Medical School Osijek, University of J.J. Strossmayer, Osijek, Croatia.
PLoS One. 2019 Jan 25;14(1):e0211433. doi: 10.1371/journal.pone.0211433. eCollection 2019.
PACAP and VIP are closely related neuropeptides with wide distribution and potent effect in the vasculature. We previously reported vasomotor activity in peripheral vasculature of male wild type (WT) and PACAP-deficient (KO) mice. However, female vascular responses are still unexplored. We hypothesized that PACAP-like activity is maintained in female PACAP KO mice and the mechanism through which it is regulated differs from that of male PACAP KO animals.
We investigated the vasomotor effects of VIP and PACAP isoforms and their selective blockers in WT and PACAP KO female mice in carotid and femoral arteries. The expression and level of different PACAP receptors in the vessels were measured by RT-PCR and Western blot.
In both carotid and femoral arteries of WT mice, PACAP1-38, PACAP1-27 or VIP induced relaxation, without pronounced differences between them. Reduced relaxation was recorded only in the carotid arteries of KO mice as compared to their WT controls. The specific VPAC1R antagonist completely blocked the PACAP/VIP-induced relaxation in both arteries of all mice, while PAC1R antagonist affected relaxation only in their femoral arteries.
In female WT mice, VPAC1 receptors appear to play a dominant role in PACAP-induced vasorelaxation both in carotid and in femoral arteries. In the PACAP KO group PAC1R activation exerts vasorelaxation in the femoral arteries but in carotid arteries there is no significant effect of the activation of this receptor. In the background of this regional difference, decreased PAC1R and increased VPAC1R availability in the carotid arteries was found.
PACAP 和 VIP 是密切相关的神经肽，在血管中分布广泛，作用强大。我们之前报道了雄性野生型（WT）和 PACAP 缺陷型（KO）小鼠外周血管的血管舒缩活性。然而，女性血管的反应仍未被探索。我们假设 PACAP 样活性在雌性 PACAP KO 小鼠中得以维持，其调节机制与雄性 PACAP KO 动物不同。
我们研究了 VIP 和 PACAP 同工型及其选择性阻滞剂在 WT 和 PACAP KO 雌性小鼠颈动脉和股动脉中的血管舒缩作用。通过 RT-PCR 和 Western blot 测量血管中不同 PACAP 受体的表达和水平。
在 WT 小鼠的颈动脉和股动脉中，PACAP1-38、PACAP1-27 或 VIP 诱导舒张，彼此之间没有明显差异。与 WT 对照组相比，KO 小鼠仅在颈动脉中记录到舒张减少。特异性 VPAC1R 拮抗剂完全阻断了所有小鼠两种动脉中 PACAP/VIP 诱导的舒张，而 PAC1R 拮抗剂仅影响其股动脉的舒张。
在雌性 WT 小鼠中，VPAC1 受体似乎在颈动脉和股动脉中 PACAP 诱导的血管舒张中发挥主导作用。在 PACAP KO 组中，PAC1R 激活在股动脉中产生血管舒张，但在颈动脉中，该受体的激活没有显著影响。在这种区域性差异的背景下，发现颈动脉中 PAC1R 的减少和 VPAC1R 的增加。
