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Protons modulate perivascular axo‐axonal neurotransmission in the rat mesenteric artery
Author(s) -
Takatori Shingo,
Hirai Kazuhiro,
Ozaki Shuichiro,
Tangsucharit Panot,
FukushimaMiyashita Satoko,
Goda Mitsuhiro,
HashikawaHobara Narumi,
Ono Nobufumi,
Kawasaki Hiromu
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12878
Subject(s) - guanethidine , chemistry , vasodilation , calcitonin gene related peptide , capsaicin , capsazepine , mesenteric arteries , endocrinology , medicine , vasoconstriction , stimulation , trpv1 , receptor , transient receptor potential channel , neuropeptide , artery , biochemistry
Background and Purpose Previous studies have demonstrated that nicotine releases protons from adrenergic nerves via stimulation of nicotinic ACh receptors and activates transient receptor potential vanilloid‐1 ( TRPV 1) receptors located on calcitonin gene‐related peptide ( CGRP )‐containing ( CGRP ergic) vasodilator nerves, resulting in vasodilatation. The present study investigated whether perivascular nerves release protons, which modulate axon‐axonal neurotransmission. Experiment Approach Perfusion pressure and pH levels of perfusate in rat‐perfused mesenteric vascular beds without endothelium were measured with a pressure transducer and a pH meter respectively. Key Results Periarterial nerve stimulation (PNS) initially induced vasoconstriction, which was followed by long‐lasting vasodilatation and decreased pH levels in the perfusate. Cold‐storage denervation of the preparation abolished the decreased pH and vascular responses to PNS . The adrenergic neuron blocker guanethidine inhibited PNS ‐induced vasoconstriction and effects on pH, but not PNS ‐induced vasodilatation. Capsaicin ( CGRP depletor), capsazepine and ruthenium red ( TRPV 1 inhibitors) attenuated the PNS ‐induced decrease in pH and vasodilatation. In denuded preparations, ACh caused long‐lasting vasodilatation and lowered pH; these effects were inhibited by capsaicin pretreatment and atropine, but not by guanethidine or mecamylamine. Capsaicin injection induced vasodilatation and a reduction in pH, which were abolished by ruthenium red. The use of a fluorescent pH indicator demonstrated that application of nicotine, ACh and capsaicin outside small mesenteric arteries reduced perivascular pH levels and these effects were abolished in a Ca 2+ ‐free medium. Conclusion and Implication These results suggest that protons are released from perivascular adrenergic and CGRP ergic nerves upon PNS and these protons modulate transmission in CGRP ergic nerves.