The Role of Pre-junctional D2-like Receptors Mediating Quinpirole-Induced Inhibition of the Vasodepressor Sensory CGRPergic Out-flow in Pithed Rats

Calcitonin gene-related peptide (CGRP) released from perivascular sensory nerves plays a role in the regulation of vascular tone. Indeed, electrical stimulation of the perivascular sensory out-flow in pithed rats produces vasodepressor responses, which are mainly mediated by CGRP release. This study investigated the potential role of dopamine D-1-like and D-2-like receptors in the inhibition of these vasodepressor responses. For this purpose, male Wistar pithed rats (pre-treated i.v. with 25mg/kg gallamine and 2mg/kgmin. hexamethonium) received i.v. continuous infusions of methoxamine (20g/kgmin.) followed by physiological saline (0.02ml/min.), the D-1-like receptor agonist SKF-38393 (0.1-1g/kgmin.) or the D-2-like receptor agonist quinpirole (0.03-10g/kgmin.). Under these conditions, electrical stimulation (0.56-5.6Hz; 50V and 2ms) of the thoracic spinal cord (T-9-T-12) resulted in frequency-dependent vasodepressor responses which were (i) unchanged during the infusions of saline or SKF-38393 and (ii) inhibited during the infusions of quinpirole (except at 0.03g/kgmin.). Moreover, the inhibition induced by 0.1g/kgmin. quinpirole (which failed to inhibit the vasodepressor responses elicited by i.v. bolus injections of exogenous -CGRP; 0.1-1g/kg) was (i) unaltered after i.v. treatment with 1ml/kg of either saline or 5% ascorbic acid and (ii) abolished after 300g/kg (i.v.) of the D-2-like receptor antagonists haloperidol or raclopride. These doses of antagonists (enough to completely block D-2-like receptors) essentially failed to modify per se the electrically induced vasodepressor responses. In conclusion, our results suggest that quinpirole-induced inhibition of the vasodepressor sensory CGRPergic out-flow is mainly mediated by pre-junctional D-2-like receptors.