Summary
Pre- and postsynaptic α-adrenergic effects of phenylephrine and tramazoline were studied in hindlegs of rabbits. The legs were autoperfused at a constant rate of flow. Phenylephrine and tramazoline were infused intraarterially. Increases in perfusion pressure evoked by the drugs were taken to represent activation of postsynaptic α-adrenoceptors. Inhibition of the pressor response to low frequency stimulation of the lumbar sympathetic chain (1 and 2 Hz) without a decrease of the response to intraarterial injection of low doses of noradrenaline (60–450 ng) was considered to reflect activation of presynaptic α-adrenoceptors.
Phenylephrine produced vasoconstriction at concentrations of 10−7–3×10−6 M. Phenylephrine 10−7 and 3×10−7 M did not change pressor responses to nerve stimulation or noradrenaline, whereas higher concentrations selectively inhibited the effect of nerve stimulation. The maximal inhibition amounted to about 30%. Tramazoline caused vasoconstriction at concentrations of 3×10−8–10−6 M. All these concentrations, and also the lower concentration of 10−8 M, diminished the response to nerve stimulation without a change in the effect of injected noradrenaline. The inhibition maximally amounted to about 80%. The sum of the vasoconstrictor effects of phenylephrine and of nerve stimulation exceeded the effect of nerve stimulation alone, whereas the sum of the vasoconstrictor effects of low concentrations of tramazoline and of nerve stimulation was lower than the effect of nerve stimulation alone. Except for tramazoline 10−6 M, the effects were limited to the leg that received the intraarterial infusion; there was no change in the contralateral leg.
The results are compatible with the view that not only in vitro, but also in vivo pre- and postsynaptic α-adrenoceptors show different pharmacological properties. In the hindleg vasculature of the rabbit as well as in some other tissues tramazoline preferentially activates the presynaptic, whereas phenylephrine preferentially activates the postsynaptic receptors. There is not sufficient evidence, however, to allow generalization of these findings and to consider all presynaptic α-adrenoceptors as one pharmacologically homogeneous group and all postsynaptic α-adrenoceptors as the second, distinct homogeneous group.
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Steppeler, A., Tanaka, T. & Starke, K. A comparison of pre- and postsynaptic α-adrenergic effects of phenylephrine and tramazoline on blood vessels of the rabbit in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 304, 223–230 (1978). https://doi.org/10.1007/BF00507962
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DOI: https://doi.org/10.1007/BF00507962