8 research outputs found
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. Because ergotamine inhibits these neurogenic vascular responses
and displays affinity for monoaminergic receptors that inhibit neurotransmitter
release, we 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–1 min–1). Thoracic
T9–T12 electrical stimulation or an intravenous
bolus of α-CGRP resulted in decreases in DBP. Ergotamine inhibited
the electrically induced, but not α-CGRP-induced, responses.
The vasodilator sensory inhibition by 3.1 μg of ergotamine kg–1 min–1 was resistant to simultaneous
blockade of 5-HT1B/1D, D2-like, and α2-adrenergic receptors upon addition of antagonists GR127935,
haloperidol, and rauwolscine. Moreover, the inhibition by 0.31 ÎĽg
of ergotamine kg–1 min–1 was unaltered
by GR127935 and haloperidol, partly blocked by GR127935 and rauwolscine
or rauwolscine and haloperidol, and abolished by GR127935, haloperidol,
and rauwolscine. These findings imply that prejunctional 5-HT1B/1D, D2-like, and α2-adrenergic
receptors mediate the sensory inhibition induced by 0.31 ÎĽg
of ergotamine kg–1 min–1, whereas
larger doses may involve other receptors. Thus, ergotamine’s
ability to inhibit the perivascular sensory peptidergic drive may
result in facilitation of its systemic vasoconstrictor properties