VPAC1 receptors play a dominant role in PACAP-induced vasorelaxation in female mice.
Animals
Carotid Arteries
/ drug effects
Female
Femoral Artery
/ drug effects
Insect Proteins
/ pharmacology
Mice
Mice, Knockout
Nitroprusside
/ pharmacology
Pituitary Adenylate Cyclase-Activating Polypeptide
/ deficiency
Receptors, Vasoactive Intestinal Polypeptide, Type I
/ antagonists & inhibitors
Vasoactive Intestinal Peptide
/ pharmacology
Vasodilation
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
29
09
2018
accepted:
14
01
2019
entrez:
26
1
2019
pubmed:
27
1
2019
medline:
28
10
2019
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Identifiants
pubmed: 30682157
doi: 10.1371/journal.pone.0211433
pii: PONE-D-18-28416
pmc: PMC6347420
doi:
Substances chimiques
Insect Proteins
0
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Receptors, Vasoactive Intestinal Polypeptide, Type I
0
maxadilan protein, insect
135374-80-0
Nitroprusside
169D1260KM
Vasoactive Intestinal Peptide
37221-79-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0211433Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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