Activation of Dopamine D3 Receptor Subtypes Inhibits the Neurogenic Systemic Vasodilation Induced by Stimulation of the Perivascular CGRPergic Discharge.

Abstract:

:The sensory nervous system controls cardiovascular homeostasis via capsaicin-sensitive neurons that release calcitonin gene-related peptide (CGRP), which subsequently activates CGRP receptors. How this perivascular CGRPergic discharge is modulated, nevertheless, remains unclear. In pithed rats, systemic vasodilation induced by CGRPergic discharge stimulation results in diastolic blood pressure (BP) decrements that are inhibited by the dopamine D2-like receptor agonist quinpirole. Since this inhibition is mediated by raclopride- or haloperidol-sensitive D2-like receptors (comprising the D2, D3, and D4 subtypes), the present study pharmacologically investigated the specific contribution of these subtypes to the modulation of the systemic CGRPergic vasodilation, using highly specific antagonists. To that end, 55 male Wistar rats were pithed for thoracic (T9-T12) spinal stimulation of the perivascular CGRPergic discharge. The resulting frequency-dependent decrements in diastolic BP were inhibited by quinpirole, and this sensory-inhibition was (a) unchanged after i.v. injections of the antagonists L-741,626 (D2) or L-745,870 (D4) and (b) completely blocked by SB-277011-A (D3). Accordingly, we suggest the main role of the D3 receptor subtypes in the inhibition by quinpirole of the neurogenic CGRPergic systemic vasodilation. These findings contribute to a better understanding of the dopaminergic modulation of the rat perivascular CGRPergic discharge producing systemic vasodilation.

journal_name

ACS Chem Neurosci

authors

Manrique-Maldonado G,Altamirano-Espinoza AH,Rivera-Mancilla E,Hernández-Abreu O,Villalón CM

doi

10.1021/acschemneuro.9b00277

subject

Has Abstract

pub_date

2019-08-21 00:00:00

pages

3751-3757

issue

8

issn

1948-7193

journal_volume

10

pub_type

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