Effect of opioid receptor antagonists on vasodilator nerve actions in the perfused rat mesentery

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Abstract

Our previous work suggests that opioid peptidcs modulate sensory nerves in the perfused rat mesentery. Therefore we tested the hypothesis that opioids are involved in the ongoing regulation of sensory nerve activity using selective opioid receptor antagonists. In the presence of guancthidinc and methoxamine, transmural nerve stimulation caused a vasodilator response which was potentiated significantly by naloxonc (3 × 10 −3 M). However, naloxone did not affect vasodilator responses to exogenous calcitonin gene related peptide. ICI 174.864 (3 × 10−7 M), a selective δ receptor antagonist, had no effect on vasodilator responses to transmural nerve stimulation. In contrast CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phc-Thr-NH2) (3 × 10−7 M), a selective μ receptor antagonist, significantly inhibited vasodilator responses to transmural nerve stimulation, effects which were abolished by naloxone treatment. In preparations prctrcalcd with β-FNA (β-funaltrexaminc HCI). an irreversible μ. receptor antagonist, naloxone no longer potentiated vasodilator responses to transmural nerve stimulation. These results suggest that potentiation of vasodilator responses to transmural nerve stimulation by naloxone may be due to blockade of μ receptors, resulting in a reduced inhibitory modulation by endogenous opioids. These findings support the contention that prejunctionai opioid receptors on sensory nerves may play a role in moduluting activity of the cardiovascular system.

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