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Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary vascular bed of the cat by sulotroban.

Publication ,  Journal Article
Nossaman, BD; McMahon, TJ; Ragheb, MS; Ibrahim, IN; Babycos, CR; Hood, JS; Kadowitz, PJ
Published in: Eur J Pharmacol
March 17, 1992

The effects of sulotroban (BM13.177; SK & F 95587), a thromboxane (TX) A2/endoperoxide (PGH2) receptor blocking agent on responses to the TXA2/PGH2 mimics, U46619 and U44069, were investigated in the pulmonary vascular bed of the intact-chest cat under constant flow conditions. Injections of U46619 and U44069 directly into the perfused lobar artery caused dose-related increases in lobar arterial pressure without altering left atrial pressure. Following administration of sulotroban in a dose of 5 mg/kg i.v., dose-response curves for U46619 and U44069 were shifted to the right in a parallel manner. The duration of the blocking effect of sulotroban was investigated, and responses to U46619 returned to approximately 50% of control in 120 min and were not significantly different from control 240 min after administration of the receptor antagonist. Sulotroban was without significant effect on responses to prostaglandin (PG) D2 or F2 alpha or serotonin, histamine, norepinephrine, angiotensin II or BAY K8644, an agent which enhances calcium entry. Sulotroban was without effect on responses to endothelin (ET)-1, sarafotoxin (S) 6a or S6c and platelet-activating factor (PAF). Sulotroban did not alter baseline vascular pressures in the cat and responses to the PG and TXA2/PGH2 precursor, arachidonic acid, were reduced. The present data show that sulotroban selectively blocks TXA2/PGH2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Scholars

Published In

Eur J Pharmacol

DOI

ISSN

0014-2999

Publication Date

March 17, 1992

Volume

213

Issue

1

Start / End Page

1 / 7

Location

Netherlands

Related Subject Headings

  • Sulfonamides
  • Serotonin
  • Receptors, Thromboxane
  • Receptors, Prostaglandin
  • Prostaglandins
  • Prostaglandin Endoperoxides, Synthetic
  • Platelet Activating Factor
  • Pharmacology & Pharmacy
  • Norepinephrine
  • Male
 

Citation

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Nossaman, B. D., McMahon, T. J., Ragheb, M. S., Ibrahim, I. N., Babycos, C. R., Hood, J. S., & Kadowitz, P. J. (1992). Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary vascular bed of the cat by sulotroban. Eur J Pharmacol, 213(1), 1–7. https://doi.org/10.1016/0014-2999(92)90225-s
Nossaman, B. D., T. J. McMahon, M. S. Ragheb, I. N. Ibrahim, C. R. Babycos, J. S. Hood, and P. J. Kadowitz. “Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary vascular bed of the cat by sulotroban.Eur J Pharmacol 213, no. 1 (March 17, 1992): 1–7. https://doi.org/10.1016/0014-2999(92)90225-s.
Nossaman BD, McMahon TJ, Ragheb MS, Ibrahim IN, Babycos CR, Hood JS, et al. Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary vascular bed of the cat by sulotroban. Eur J Pharmacol. 1992 Mar 17;213(1):1–7.
Nossaman, B. D., et al. “Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary vascular bed of the cat by sulotroban.Eur J Pharmacol, vol. 213, no. 1, Mar. 1992, pp. 1–7. Pubmed, doi:10.1016/0014-2999(92)90225-s.
Nossaman BD, McMahon TJ, Ragheb MS, Ibrahim IN, Babycos CR, Hood JS, Kadowitz PJ. Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary vascular bed of the cat by sulotroban. Eur J Pharmacol. 1992 Mar 17;213(1):1–7.
Journal cover image

Published In

Eur J Pharmacol

DOI

ISSN

0014-2999

Publication Date

March 17, 1992

Volume

213

Issue

1

Start / End Page

1 / 7

Location

Netherlands

Related Subject Headings

  • Sulfonamides
  • Serotonin
  • Receptors, Thromboxane
  • Receptors, Prostaglandin
  • Prostaglandins
  • Prostaglandin Endoperoxides, Synthetic
  • Platelet Activating Factor
  • Pharmacology & Pharmacy
  • Norepinephrine
  • Male