Intrathecal administration of delta receptor agonists in the urethane anesthetized rat provokes an increase in arterial pressure via a non-opioid mechanism

doi:10.1016/0006-8993(90)90635-O

Brain Research

Volume 512, Issue 2, 2 April 1990, Pages 259-268

https://doi.org/10.1016/0006-8993(90)90635-O Get rights and content

Abstract

Intrathecal administration of the delta receptor specific agonists Leu⁵-enkephalin (Leu-Enk; 300 nmol), Met⁵-enkephalin (Met-Enk; 300 nmol) and [d-Pen², dPen⁵] enkephalin (DPDPE; 100 nmol) to the T₂ or the T₉ segment of the rat spinal cord provoked a transient < 5min increase (15–20 mm Hg) in arterial pressure. DPDPE, but not Leu-Enk, also significantly increased heart rate by 30–35 bpm. Intravenous administration of 300 nmol of Leu-Enk mimicked the effect observed following intrathecal administration. The hypertensive effect of intrathecal and intravenous Leu-Enk administration was blocked by prior systemic administration (10 mg/kg) of the nicotinic ganglion blocker hexamethonium, suggesting that the effect was mediated via sympathetic activation. The increase in arterial pressure observed following intrathecal Leu-Enk administration was not blocked by either intrathecal (305 nmol) or intravenous (10 mg/kg) administration of the opiate receptor blocker naloxone, although naloxone did block the hypertension provoked by intravenous (10 mg/kg) administration. Moreover, intrathecal administration of Des-Tyr¹-Leu-Enk (300 nmol), an enkephalin fragment devoid of opiate receptor activity, also increased arterial pressure. These results suggest that the hypertension elicited by intrathecal delta agonist administration was not mediated via an opioid mechanism.

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Studies have indicated that GABA tonically inhibits cardiovascular (Gordon, 1985; Hong and Henry, 1990) as well as cervical and splanchnic sympathetic outflows (Goodchild et al., 2008), however whether other functionally distinct outflows are similarly inhibited have yet to be determined. On the other hand, intrathecal injection of opioid agonists have yielded conflicting results, with pressor, depressor or a lack of cardiovascular responses described with responses appearing to vary dependent upon drug and state of anaesthesia (Li et al., 1988; Rochford and Henry, 1990). Whether or not there is tonic modulation of sympathetic outflows by enkephalin has only been minimally explored (Ang et al., 1999).
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Intrathecal administration of delta receptor agonists in the urethane anesthetized rat provokes an increase in arterial pressure via a non-opioid mechanism

Abstract

Eur. J. Pharmacol.

Brain Research

Brain Research

Eur. J. Pharmacol.

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Neuroscience

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