Effects of the new thromboxane A2 antagonist vapiprost on isolated canine blood vessels.

Abstract

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.

• Authors: T Matsuzaki, K Noguchi, J Nakasone, K Uezu, M Higuchi, M Sakanashi
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 42 Issue 11 Pg. 1318-22 (Nov 1992) ISSN: 0004-4172 [Print] Germany
• PMID: 1492844 (Publication Type: Journal Article)

Chemical References

• Biphenyl Compounds
• Heptanoic Acids
• Prostaglandin Endoperoxides, Synthetic
• Receptors, Prostaglandin
• Vasoconstrictor Agents
• Thromboxane A2
• Potassium Chloride
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Dinoprost
• vapiprost
• Norepinephrine

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Animals
• Biphenyl Compounds (pharmacology)
• Dinoprost (pharmacology)
• Dogs
• Female
• Heptanoic Acids (pharmacology)
• In Vitro Techniques
• Male
• Muscle Contraction (drug effects)
• Muscle Relaxation (drug effects)
• Muscle, Smooth, Vascular (drug effects)
• Norepinephrine (pharmacology)
• Potassium Chloride (pharmacology)
• Prostaglandin Endoperoxides, Synthetic (pharmacology)
• Receptors, Prostaglandin (antagonists & inhibitors)
• Thromboxane A2 (antagonists & inhibitors)
• Vasoconstrictor Agents (pharmacology)