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.
MeSH terms
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Animals
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Arginine / analogs & derivatives
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Arginine / pharmacology
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Blood Pressure* / drug effects
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Endothelin Receptor Antagonists
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Hypertension / physiopathology*
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NG-Nitroarginine Methyl Ester
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Nitric Oxide Synthase / antagonists & inhibitors
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Peptides, Cyclic / pharmacology
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Pyrimidines / pharmacology*
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Rats
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Rats, Inbred SHR
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Rats, Inbred WKY
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Receptor, Endothelin B
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Receptors, Endothelin / physiology*
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Sulfonamides / pharmacology*
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Viper Venoms / pharmacology
Substances
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Endothelin Receptor Antagonists
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Peptides, Cyclic
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Pyrimidines
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Receptor, Endothelin B
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Receptors, Endothelin
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Ro 46-8443
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Sulfonamides
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Viper Venoms
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sarafotoxins s6
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Arginine
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Nitric Oxide Synthase
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cyclo(Trp-Asp-Pro-Val-Leu)
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NG-Nitroarginine Methyl Ester