The effects of morphine, nalbuphine, and butorphanol on adrenergic function in canine saphenous veins.

Abstract:

:Saphenous vein rings mounted in organ chambers containing Krebs-Ringer solution were used to determine if the venodilator effects of morphine, nalbuphine, and butorphanol are the result of interference with adrenergic neurotransmission or are caused by direct depressant actions on venous smooth muscle cells. Morphine (5 X 10(-5) M and 2 X 10(-4) M) caused a dose-dependent depression of the contractile response to transmural electrical stimulation. H1- and H2- histamine antagonists did not attenuate the inhibitory effect of morphine. Concentrations of morphine and nalbuphine lower than 5 X 10(-5) M had no effect, whereas 5 X 10(-6) M butorphanol significantly depressed the evoked tension response to electrical stimulation. The contractile responses of the veins to exogenous norepinephrine (NE) were not altered by morphine, indicating a presynaptic site of action rather than a direct action on the venous smooth muscle. Transmural electrical stimulation was used to evoke release of endogenous NE. Morphine (5 X 10(-5) M and 2 X 10(-4) M), nalbuphine (2 X 10(-4) M), and butorphanol (4 X 10(-6) M) significantly decreased release of NE. Naloxone did not alter NE release and did not attenuate the inhibition of NE release observed with the opiates, indicating that the effect of morphine on this neuroeffector junction is not mediated by a naloxone-sensitive opiate receptor. Blockade of presynaptic alpha receptors by phenoxybenzamine or phentolamine augments NE release caused by transmural electrical stimulation; morphine inhibited this augmentation. The results of these experiments indicate that high concentrations of morphine may decrease NE release, an effect that may contribute to the venodilation and hypotension observed following administration of high doses of morphine in humans. In the usual analgesic doses, the venodilatory effects of morphine cannot be explained by local action on either NE release or venous smooth muscle contractility.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Muldoon S,Otto J,Freas W,Watson RL

subject

Has Abstract

pub_date

1983-01-01 00:00:00

pages

21-8

issue

1

eissn

0003-2999

issn

1526-7598

journal_volume

62

pub_type

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