AN OPIOID PEPTIDE INHIBITS CAPSAICIN-SENSITIVE VASODILATATION IN THE PIGS SKIN

Microcirculatory effects of electrical stimulation of nerves through a pair of needle electrodes in the skin of anaesthetized pigs were studied by using the laser Doppler flowmetric method. Electrical stimulation (0.3-30 Hz) evoked a short-lasting decrease in capillary blood flux (vasoconstriction) followed by an increase (vasodilatation), of longer duration. Vasoconstriction was inhibited by local guanethidine, but not by capsaicin pretreatment, whereas vasodilatation was blocked by local capsaicin, but not by guanethidine. Both phases of the response were suppressed by local application of tetrodotoxin. Thus, vasoconstriction due to electrical stimulation seems to be of sympathetic origin, while vasodilatation is a result of a release of vasoactive substances from capsaicin-sensitive nerve endings. Vasodilatation due to electrical stimulation was strongly and dose-dependently inhibited by the opioid peptide [D-Met2, Pro5] enkephalinamide, while vasoconstriction remained apparently unchanged. At both doses of the opioid peptide tested (0.03 and 0.15 mumol/kg i.m.) inhibition of vasodilatation was larger at lower than at higher frequencies of stimulation. Guanethidine pretreatment did not influence the inhibitory action of [D-Met2, Pro5] enkephalinamide. Naloxone (1.5 mumol/kg i.m.) reversed or prevented the inhibitory action of the opioid peptide; naloxone on its own did not influence responses due to 0.3-30 Hz stimulation. [D-Met2, Pro5] enkephalinamide (0.15 mumol/kg i.m.) did not influence basal blood flux in the skin, mean arterial blood pressure, respiratory minute volume or respiratory frequency. It was concluded that stimulation of opioid receptors by [D-Met2, Pro5] enkephalinamide is likely to inhibit stimulation-evoked vasodilatation by reducing the release of vasoactive substances from capsaicin-sensitive afferent neurons, an effect that does not depend on functional integrity of sympathetic nerves. Endogenous opioids probably do not modulate the capsaicin-sensitive vasodilatation.