Sulotroban selectively inhibits thromboxane-receptor-mediated responses in the peripheral vascular bed of the cat. 1992

P Kvamme, and R K Minkes, and P J Kadowitz
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.

The effects of Sulotroban (BM 13.177, SK&F 95587) were investigated under conditions of controlled blood flow in the hindquarters and mesenteric vascular beds of the cat. Injections of the thromboxane (TX) A2 mimics, U46619 and U44069, caused dose-related increases in perfusion pressure. After administration of SK&F 95587, vasoconstrictor responses to the TXA2 mimics were reduced significantly, and the dose-response curves were shifted to the right in a parallel fashion. Responses to norepinephrine, phenylephrine, tyramine, endothelin-1, angiotensin II, BAY K8644, acetylcholine, sodium nitroprusside, isoproterenol, lemakalim, prostaglandin (PG) E1, and PGF2 alpha, agents which alter vascular resistance by a variety of mechanisms, were not changed by the TXA2 receptor antagonist. However, SK&F 95587 reduced mesenteric vasoconstrictor responses to PGD2. Results of the present study indicate that SK&F 95587 blocks TX-receptor-mediated responses in the hindquarters circulation of the cat in a competitive and selective manner and reduces mesenteric vascular responses to the TXA2 mimics, as well as PGD2. These data suggest that this antagonist would be useful in studies on the role of TXA2 in physiologic and pathophysiologic processes in the systemic vascular bed of the cat.

UI MeSH Term Description Entries
D008297 Male Males
D008643 Mesentery A layer of the peritoneum which attaches the abdominal viscera to the ABDOMINAL WALL and conveys their blood vessels and nerves. Mesenteries
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D005260 Female Females
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006614 Hindlimb Either of two extremities of four-footed non-primate land animals. It usually consists of a FEMUR; TIBIA; and FIBULA; tarsals; METATARSALS; and TOES. (From Storer et al., General Zoology, 6th ed, p73) Hindlimbs
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D017482 Receptors, Thromboxane Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems. TP Receptors,Thromboxane Receptors,Receptors, Thromboxanes,TP Receptor,Thromboxane Receptor,Receptor, TP,Receptor, Thromboxane,Receptors, TP,Thromboxanes Receptors

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