Effects of the new thromboxane A2 antagonist vapiprost on isolated canine blood vessels.
Effects of the new thromboxane A2 antagonist vapiprost (SN-309, GR-32191B, CAS 85505-64-2) on isolated canine blood vessels were investigated. U46619 ((15S)-hydroxy-11a, 9a-(epoxymethano) prosta-5Z, 13E-dienoic acid) 10(-10)-10(-6) mol/l, a thromboxane A2 analogue, produced concentration-dependent contractions of oblong or ring preparations isolated from basilar, coronary, mesenteric and femoral arteries. Vapiprost 10(-8) and 10(-7) mol/l significantly and concentration-dependently shifted the concentration-contraction curves for U46619 of these arteries to the right. The pA2 values were 8.80 +/- 0.09 in basilar arteries, 8.67 +/- 0.12 in coronary arteries, 8.86 +/- 0.05 in mesenteric arteries and 9.01 +/- 0.07 in femoral arteries. On the other hand, oblong or ring preparations of basilar, coronary, mesenteric and femoral arteries showed sustained contractile responses to KCl 3 x 10(-2) mol/l, U46619 10(-7) mol/l or prostaglandin (PG) F2 alpha 10(-5) mol/l. Norepinephrine (NE) 3 x 10(-5) mol/l also produced sustained contractions in mesenteric and femoral arterial preparations, but not in basilar and coronary arterial preparations. Vapiprost 10(-10)-3 x 10(-6) mol/l relaxed these four arterial preparations constricted with U46619 10(-7) mol/l and PGF 2 alpha 10(-5) mol/l in a concentration-dependent fashion, but hardly affected them constricted with KCl 3 x 10(-2) mol/l. NE 3 x 10(-5) mol/l-induced contractures of mesenteric and femoral arterial preparations were not influenced by any concentrations of vapiprost. Results indicate that vapiprost has an antagonistic action on a so-called TP-receptor and/or a vasoconstrictive prostaglandin(s)-receptor and thus produces vasorelaxation.
Matsuzaki
T
T
Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Noguchi
K
K
Nakasone
J
J
Uezu
K
K
Higuchi
M
M
Sakanashi
M
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; C060013:vapiprost; D009638:Norepinephrine