Inhibition of endothelin (ET-1) induced pressor responses by the endothelin (ETA) receptor antagonist FR139317 in the pithed rat.
The effects of the novel ETA receptor antagonist, FR 139317, on ET-1 induced blood pressure changes were studied in the pithed Sprague-Dawley rat. FR139317 in a dose of 0.025 mg/kg b.w. had no effect while 0.05-1 mg/kg b.w. dose dependently inhibited the pressor response to an i.v. bolus injection of ET6-1 (800 pmoles/kg). While FR139317 potently inhibited the magnitide and duration of the ET-1 induced pressor response, the ETA antagonist did not significantly influence the shortlasting initial depressor response. We conclude that FR139317 in the pithed rat potently inhibits ET-1 mediated pressor responses and that this agent may become a significant tool to elucidate the putative physiological and pathophysiological role of ETA receptor mediated responses.
Department of Pharmacology and Clinical Pharmacology, University of Göteborg, Sweden.
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Sun
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Hedner
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Feng
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Edvinsson
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; C079574:FR 139317