Summary
Rabbit isolated ear arteries were perfused at a constant flow and stimulated with field pulses (5 Hz, 5 impulses). Different tachykinins and capsaicin depressed stimulation-induced vasoconstriction, substance P (SP) being the most potent inhibitor. The rank order of potency of the tachykinins was, SP ∼ physalaemin ∼ eledoisin>SP-methylester; that of SP and its C-terminal fragments, SP∼SP-(2–11)∼SP-(4–11)>SP-(6–11). SP-(1–9) was inactive. The SP antagonist (Arg5,d-Trp7,9,Nle11)SP-(5–11) 10 μmol/l shifted the concentration-response curve of SP to the right (pA2=5.43), whereas it did not reduce the action of capsaicin. Another SP antagonist (d-Pro4,d-Trp7,9,10)SP-(4–11) 10 μmol/l failed to affect the SP depression. Neither antagonist changed vasoconstriction by itself. Pretreatment of the arteries with a mixture of yohimbine, propranol, atropine, diphenhydramine, burimamide, methysergide and indomethacin, all 1 μmol/l, did not influence the effect of SP or capsaicin. Only the inhibition by SP, but not that by capsaicin was abolished after mechanical destruction of the endothelium. SP, physalaemin and eledoisin, all 3 μmol/l, reduced vasoconstriction by noradrenaline or histamine; capsaicin 30 μmol/l depressed noradrenaline-induced vasoconstriction. In arteries preincubated with3H-noradrenaline, electrical stimulation (1 Hz, 120 pulses) triggered an increase in the outflow of tritium and evoked vasoconstriction. SP 1 μmol/l did not change either basal or stimulation-evoked tritium outflow, whereas it reduced vasoconstriction. In conclusion, SP depresses nerve stimulation-induced vasoconstriction solely by changing smooth muscle contractility; the receptor activated seems to belong to the SP-P type. Under the conditions of these experiments there is no indication for a similar effect of endogenous SP.
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Illes, P., Falkenhausen, S.v. Functional characterization of substance P receptors in the rabbit ear artery. Naunyn-Schmiedeberg's Arch. Pharmacol. 333, 52–58 (1986). https://doi.org/10.1007/BF00569660
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DOI: https://doi.org/10.1007/BF00569660