Effects of some isoprostanes on the human umbilical arteryin vitro

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Abstract
Cumulative concentration‐effect curves for the selective prostanoid TP receptor agonist U46619 and six isoprostanes were constructed in the human isolated umbilical artery. All compounds except 8‐iso‐PGF3α produced concentration‐dependent contractions. The contractile response to the isoprostanes increased with each cumulative addition up to a point, after which subsequent addition reduced the contraction below the previous level. This [downturn] in the concentration‐effect curve did not occur with U46619. The potencies of the compounds tested were as follows (pEC50±s.e.mean): U46619, 6.7±0.2; 8‐iso‐PGE2, 6.5±0.1; 8‐iso‐PGF2α, 5.8±0.2; 8‐iso‐PGE1, 5.4±0.1; 8‐iso‐PGF1α, 5.0±0.1; 8‐iso‐PGF2β> 4.8; 8‐iso‐PGF3α>> 4.8 (n=4–17). Neither 8‐iso‐PGF2β nor 8‐iso‐PGF3α at 44 μM had a significant effect on cumulative concentration‐effect curves to U46619. The selective TP receptor antagonist GR32191 (0.1 μM) caused rightward shifts in the concentration‐effect curves to all the active compounds. pA2 values for GR32191 against U46619, 8‐iso‐PGE2, 8‐iso‐PGF2α, 8‐iso‐PGE1 were 7.6±0.2, 9±1, 8.2±0.3 and 7.7±0.3, respectively (n=4). Neither Nω‐nitro‐L‐arginine methyl ester (100 μM) nor the selective DP receptor antagonist BW A868C (50 nM) affected the complex concentration‐effect curve to 8‐iso‐PGE2 (n=3). Stable contractions to U46619 (1–3 μM) were unaffected by anandamide at concentrations up to 60 μM. British Journal of Pharmacology (2000) 129, 509–514; doi:10.1038/sj.bjp.0703083