Inhibitory effects of dynorphin on electric field stimulation induced contraction of blood vessels in vitro

The direct effects of opioid peptides on blood vessels were observed on rabbit ear arteries and dog mesenteric arteries isolated. The contraction of rabbit ear arteries induced by electric field stimulation was markedly inhibited by dynorphin1-13, a kappa agonist, with an IC50 of 0.085 μM (n=7). D-ala2-met5-enkephalin was less effective (IC50=1μ M, n=5), and Dala2-D-leu5-enkephalin, a delta agonist, or metorphamide, a mu agonist, was ineffective with concentration as high as 1 μM (n=6 and 3, respectively). The stimulationinduced contraction of dog mesenteric arteries was reduced by dynorphin1-13(IC50=0.51μM, n=8) and metorphamide (IC50=1μM, n=7), but was not affected by D-ala2-met5-enkephalin or D-ala2-Dleu5-enkephalin under concentrations up to 1 μM(n=6 and 5, respectively). Naloxone reversed effects of these opioid peptides with very different potencies, the order of the potencies was: metorphamide>D-ala2-met5-enkephalin>dynorphin. Dynorphin1-13(5Μm, n=11) did not alter the basal tension of blood vessels, nor the contraction induced by norepinephrine (0.05-0.4μM), both contractions were markedly inhibited by phentolamine, an α-adrenergic blocker. These results suggest that opioids can directly act on opiate rectptors(mainly kappa subtype) of blood vessel. Dynorphin o f blood vessel. Dynirphin reduces the stimulation-induced contraction of blood vessels probably by a presynaptic inhibition of norepinephrine release from nerve terminals.