Functional characterization of the prejunctional receptors mediating the inhibition by ergotamine of the rat perivascular sensory peptidergic drive.

Calcitonin gene-related peptide (α-CGRP) released from perivascular sensory nerves induces decreases in diastolic blood pressure (DBP). Experimentally, this can be shown by spinal thoracic (T9-T12) electrical stimulation of these afferent fibers. Since ergotamine inhibits these neurogenic vascular responses and displays affinity for monoaminergic receptors that inhibit neurotransmitter release, the present study investigated whether this ergotamine-induced inhibition results from activation of serotonin 5-HT1B/1D, dopamine D2-like and α2-adrenergic receptors. Wistar rats were pithed and, under autonomic ganglion blockade, received intravenous infusions of methoxamine followed by ergotamine (0.1-3.1 µg/kg.min). Thoracic T9-T12 electrical stimulation or intravenous bolus of α CGRP resulted in decreases in DBP. Ergotamine inhibited the electrically-induced, but not of the α-CGRP-induced, responses. The vasodilator sensory-inhibition by 3.1 μg/kg.min ergotamine was resistant to simultaneous blockade of 5-HT1B/1D, D2-like and α2-adrenergic receptors by giving the antagonists GR127935+haloperidol+rauwolscine. Moreover, the inhibition by 0.31 μg/kg.min ergotamine was unaltered by GR127935+haloperidol, partly blocked by GR127935+rauwolscine or rauwolscine+haloperidol, and abolished by GR127935+haloperidol+rauwolscine. These findings imply that prejunctional 5-HT1B/1D, D2-like and α2-adrenergic receptors mediate the sensory-inhibition induced by 0.31 µg/kg.min ergotamine, whereas higher doses may involve other receptors. Thus, ergotamine's capability to inhibit the perivascular sensory peptidergic drive may result in a facilitation of its systemic vasoconstrictor properties.