The Effects of Naloxone on Canine Splanchnic Arterial Smooth Muscle

Abstract

The pharmacological properties of naloxone on vascular smooth muscle in vitro were examined using canine mesenteric arterial segments. Naloxone exerted two different effects on the artery: (A) naloxone at a high concentration (3 × 10^-4 M) produced a nonspecific vasodilation; and (B) naloxone at lower concentrations (3 × 10^-7, 3 × 10^-6, and 3 × 10^-5 M) augmented the vasoconstrictor effects of epinephrine and norepinephrine without altering KCl-or serotonin-induced constriction. Naloxone's augmenting effect on epinephrine-induced constriction was dose dependent. Even when the arterial strips were incubated in low calcium (0.8 mM) or calcium free Kreb's solution, naloxone (3 × 10^-5 M) still augmented epinephrine-induced constriction. With respect to naloxone's effect on another α-adrenoreceptor agonist, naloxone (3 × 10^-5 M) failed to alter phenylephrine-induced constriction. Naloxone's augmenting effect on norepinephrine-induced constriction was abolished when the specimens were incubated with 10^-5 M normetanephrine, while naloxone (3 × 10^-5 M) still augmented the constriction even when the specimens were incubated with 10^-5 M cocaine. These results suggest that naloxone at lower concentrations may augment the constrictor responses to catecholamines, at least in part, by inhibiting the extraneuronal uptake of those catecholamines.