Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice

J Vasc Res. 2017;54(6):359-366. doi: 10.1159/000481781. Epub 2017 Nov 9.

Abstract

Pituitary adenylate cyclase-activating peptide (PACAP; 1-38 and 1-27) and vasoactive intestinal peptide (VIP) are related neuropeptides of the secretin/glucagon family. Overlapping signaling through G-protein-coupled receptors mediates their vasomotor activity. We previously showed that PACAP deficiency (PACAP-KO) shifts the mechanisms of vascular response and maintains arterial relaxation through the VIP backup mechanism and (mainly) its VPAC1R, but their age-dependent modulation is still unknown. We hypothesized that backup mechanisms exist, which maintain the vasomotor activity of these peptides also in older age. Thus, we investigated the effects of exogenous VIP and PACAP peptides in isolated carotid arteries of 2- and 15-month-old wild-type (WT) and PACAP-KO mice. All peptides induced relaxation in the arteries of young WT mice, whereas in young PACAP-KO mice PACAP1-27 and VIP, but not PACAP1-38, induced relaxation. Unlike VIP, PACAP-induced vasomotor responses were reduced in aging WT mice. However, in the arteries of aging PACAP-KO mice, PACAP1-27- and VIP-induced responses were reduced, but PACAP1-38 showed a greater vasomotor response compared to that of young PACAP-KO animals. There were no significant differences between the vasomotor responses of aging WT and PACAP-KO mice. Our data suggest that, in the absence of PACAP both in young and old ages, the vascular response is mediated through backup mechanisms, most likely VIP, maintaining proper vascular relaxation in aging-induced PACAP insufficiency.

Keywords: Carotid artery; Neuropeptides; PACAP-KO mice; Relaxation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Carotid Artery, Common / drug effects*
  • Carotid Artery, Common / physiology
  • Dose-Response Relationship, Drug
  • Genotype
  • In Vitro Techniques
  • Male
  • Mice, Knockout
  • Phenotype
  • Pituitary Adenylate Cyclase-Activating Polypeptide / deficiency
  • Pituitary Adenylate Cyclase-Activating Polypeptide / genetics
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology*
  • Vasoactive Intestinal Peptide / pharmacology*
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*

Substances

  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Vasodilator Agents
  • Vasoactive Intestinal Peptide