The role of ETB receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ETB receptor antagonist Ro 46-8443.

Abstract

We used Ro 46-8443, non-peptidic antagonist selective of endothelin ETB receptors, to study the role of ETB receptors in rat hypertension models. In normotensive rats, Ro 46-8443 decreased blood pressure, but in SHR and DOCA rats, it induced a pressor effect, due to blockade of ETB-mediated release of nitric oxide since L-NAME prevented it. In rats rendered hypertensive by chronic L-NAME, Ro 46-8443 did not induce a pressor but depressor effect. Thus, in DOCA rats and SHR, Ro 46-8443 reveals a predominant influence of endothelial 'vasorelaxant' ETB receptors, while in normotensive rats the prevailing role of ETB receptors seems to be in mediating a vasoconstrictor tone.

• Authors: M Clozel, V Breu
• Journal: FEBS letters (FEBS Lett) Vol. 383 Issue 1-2 Pg. 42-5 (Mar 25 1996) ISSN: 0014-5793 [Print] England
• PMID: 8612787 (Publication Type: Journal Article)

Chemical References

• Endothelin Receptor Antagonists
• Peptides, Cyclic
• Pyrimidines
• Receptor, Endothelin B
• Receptors, Endothelin
• Ro 46-8443
• Sulfonamides
• Viper Venoms
• sarafotoxins s6
• Arginine
• Nitric Oxide Synthase
• cyclo(Trp-Asp-Pro-Val-Leu)
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Arginine (analogs & derivatives, pharmacology)
• Blood Pressure (drug effects)
• Endothelin Receptor Antagonists
• Hypertension (physiopathology)
• NG-Nitroarginine Methyl Ester
• Nitric Oxide Synthase (antagonists & inhibitors)
• Peptides, Cyclic (pharmacology)
• Pyrimidines (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptor, Endothelin B
• Receptors, Endothelin (physiology)
• Sulfonamides (pharmacology)
• Viper Venoms (pharmacology)