Summary
The effect of prostaglandin (PG) E2, F2α, the thromboxane A2 mimetic U46619 (9,11-dideoxy-9α,11α-methanoepoxy-prostaglandin F2α) and the prostacyclin mimetic iloprost was investigated in feline and rat pial arteries in-situ using perivascular microapplication and measurement of vascular diameter. U 46619 induced a concentration-dependent vasoconstriction with a maximal response of 24% at 10−6 mol · l−1 and an EC50 of 4.9 × 10−8 mol · l−1. This effect was inhibited by the thromboxane receptor blocking drugs AH23848B (([1α(z), 2ß,5α]-(±)-7-[5-[(1,1′-(biphenyl)-4-yl]methoxy]-2-(4-morpholinyl)-3-oxocyclo-pentyl]-4-heptenoic acid)) and EP092 ((±)-5-endo-(6′-carboxyhex-2′z-enyl)-6-exo[1′-[N-(phenylthiocarbamoyl)-hydrazano]-ethyl]-bicyclo[2,2,1]-heptane)), indicating the involvement of thromboxane-prostanoid-receptors. PGF2α produced vasodilatation in cats with an increase in vessel diameter of 30% at 10−3 mol · l−1, but constricted rat pial arteries concentration-dependently with a maximal response of 23% at 10−4 mol · l−1. PGE2 and iloprost induced concentration-dependent (10−9 ′- 10−5 mol · l−1) dilatations with apparent maximal responses of 39% and 34% at 10−5 mol · l−1, respectively. The corresponding EC50 values were 2.45 × 10−7 mol · l−1 (PGE2) and 3.5 × 10−7 mol · l−1 (iloprost). These data demonstrate the presence of prostanoid receptors mediating constriction and dilatation under in-situ conditions. Since the norepinephrine- but not the potassium-free artificial cerebrospinal fluid-induced constriction in cats was blocked by the thromboxane-prostanoid-receptor antagonists AH 23848 B and EPO 92, it is likely that the effect of norepinephrine is, at least partly, mediated by the release of an endogenous prostanoid acting at constriction-inducing thromboxane-prostanoid-receptors. This conclusion is also supported by the finding that the norepinephrine-induced constriction was significantly reduced in the presence of indomethacin.
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Wahl, M., Schilling, L. & Whalley, E.T. Cerebrovascular effects of prostanoids. Naunyn-Schmiedeberg's Arch Pharmacol 340, 314–320 (1989). https://doi.org/10.1007/BF00168516
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DOI: https://doi.org/10.1007/BF00168516