Paracrine control of mesenteric perivascular axo-axonal interaction

Area of Science:

• Neuroscience
• Vascular Biology
• Physiology

Background:

• The mesenteric arteries exhibit dense innervation by adrenergic, calcitonin gene-related peptide (CGRP)-containing (CGRPergic), and nitric oxide-containing (nitrergic) nerves.
• CGRPergic and nitrergic nerves are often found in close proximity to adrenergic nerves.

Purpose of the Study:

• To investigate the role of proton release from nerves in mediating vasodilation in rat mesenteric arteries.
• To elucidate the interaction between adrenergic, CGRPergic, and TRPV1-expressing nerves in vascular regulation.

Main Methods:

• Immunohistochemistry and double-immunostaining to identify nerve types and their associations.
• Perfusion of isolated rat mesenteric vascular beds to measure pH changes and vasodilation in response to various stimuli (nicotine, capsaicin, acetylcholine, periarterial nerve stimulation).
• Pharmacological interventions including denervation, guanethidine, and TRPV1 antagonists.

Main Results:

• Stimulation of adrenergic nerves, as well as administration of nicotine, capsaicin, and acetylcholine, induced vasodilation accompanied by a decrease in perfusate pH.
• Denervation abolished nicotine- and periarterial nerve stimulation-induced pH lowering, while guanethidine inhibited these responses but not those induced by acetylcholine or capsaicin.
• Protons were identified as mediators released from both adrenergic and CGRPergic nerves, with CGRPergic nerves utilizing exocytosis.

Conclusions:

• Adrenergic nerve activation releases protons that activate TRPV1 channels on CGRPergic nerves, leading to vasodilation.
• CGRPergic nerves release protons via exocytosis, potentially facilitating neurotransmission through a positive feedback loop.