Antagonism of prostanoid-induced vascular contraction by 13-azaprostanoic acid (13-APA).

Isometric contractions in vitro of helically cut strips of canine mesenteric arteries (O.D. = 0.6-1 mm) were recorded in the presence of 10 microM indomethacin. PGF2 alpha PGE2, U-46619 (TXA2 mimetic), norepinephrine, 5-hydroxytryptamine, and KCl produced dose-related contractions. The EC50 values of the prostanoids in the control period were: PGF2 alpha, 7.3 +/- 0.7 X 10(-7) M; PGE2, 2.1 +/- 0.2 X 10(-6) M; and U-46619, 4.1 +/- 1.0 X 10(-10) M. Exposure to 13-azaprostanoic acid (13-APA), 5 X 10(-5) M and 2 X 10(-4) M, for 20 min caused parallel and dose-related shifts to the right of the dose-response curves generated by all three prostanoids without affecting the contractile responses to KCl, norepinephrine, or 5-hydroxytryptamine or relaxation induced by PGI2. 13-APA, at the concentrations used, had no agonist activity. Small contractions (10-15%) seen on the addition of 13-APA to the baths were found to be related to the alcohol content of the solvent. Dose ratios (with/without antagonist) at the EC50 level were found to be: in the presence of 5 X 10(-5) M 13-APA PGF2 alpha, 2.7 +/- 0.3; PGE2, 3.5 +/- 0.9; U-46619, 5.2 +/- 0.9; in the presence of 2 X 10(-4) M 13-APA PGF2 alpha, 17.1 +/- 3; PGE2, greater than 50; and U-46619, 23.3 +/- 5.7. Thus, 13-APA is a specific antagonist of these prostanoids with no agonist activity of its own.