The role of ETB receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ETB receptor antagonist Ro 46-8443.
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.
Clozel
M
M
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Breu
V
V
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D006973:Hypertension / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology; D000096926:Benzenesulfonamides
D001120:Arginine; D065128:Endothelin Receptor Antagonists; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010456:Peptides, Cyclic; D011743:Pyrimidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013449:Sulfonamides; D014757:Viper Venoms; C099180:Ro 46-8443; D000096926:Benzenesulfonamides; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu)