S 17162 Is a Novel Selective Inhibitor of Big ET-1 Responses in the Rat
| Autor: | T. J. Verbeuren, V. Barou, G. De Nanteuil, Jean-Jacques Descombes, D. Versluys, P. Mennecier, Michel Laubie |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Pharmacology
medicine.medical_specialty Kidney biology Phosphoramidon Biological activity Endothelin 1 Norepinephrine (medication) chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry In vivo Enzyme inhibitor Internal medicine Renin–angiotensin system medicine biology.protein Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 26:S61-64 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/00005344-199506263-00020 |
| Popis: | Endothelin-l (ET-I) is a powerful renal vasoconstrictor peptide that may be implicated in acute renal failure. The aim of the present study was to test the effects of the novel endothelin-converting enzyme inhibitor S 17162 (N-(2,3 dihydroxy propyl phosphonyl)-(S)-Leu-(S)-Trp-OH, disodium salt) on pressor responses to ET-1 and its precursor, big ET-1, in isolated perfused rat kidneys and in pithed rats. In both models, phosphoramidon selectively inhibited the pressor responses to big ET-I without influencing those to ET-1, angiotensins (AT-I and AT-II) or norepinephrine. S 17162 was active against big ET-1 in both test systems. It selectively inhibited the pressor responses to big ET-1 with ID 50 values of 160 μg/kg/min (phosphoramidon : 120 μg/kg/min) in the spinal rat and 6 μM (phosphoramidon : 5 μM) in the perfused rat kidney. In the nonanesthetized rat, S 17162 at 20 mg/kg p.o. inhibited the pressor responses to big ET-1, demonstrating its oral bioavailability. Therefore, S 17162 is a potential candidate for development as an orally active anti-endothelin drug. |
| Databáze: | OpenAIRE |
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