Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats.

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Gardiner SM, Kemp PA, March JE, Bennett T

Effects of bosentan (Ro 47-0203), an ETA-, ETB-receptor antagonist, on regional haemodynamic responses to endothelins in conscious rats.

Br J Pharmacol. 1994 Jul;112(3):823-30.

PubMed ID

7921608 [ View in PubMed

]

Abstract

1. Regional haemodynamic responses to endothelin (ET)-1, -2 and -3 and big ET-1 (all at 500 pmol kg-1) were assessed in the same conscious Long Evans rats (n = 8) in the absence or presence of the mixed ETA-, ETB-receptor antagonist, Ro 47-0203 (bosentan; 30 mg kg-1). 2. Bosentan blocked the initial depressor, tachycardic and hindquarters hyperaemic vasodilator effects of ET-1, -2 and -3, and substantially curtailed the primary renal and secondary hindquarters vasoconstrictor responses. Bosentan did not inhibit the initial mesenteric vasoconstrictor action of ET-1, but reduced the duration of the later mesenteric vasoconstriction. In contrast, bosentan delayed the rate of onset, and reduced the duration, of the mesenteric vasoconstrictor actions of ET-2 and ET-3. The most likely explanation of this finding is that ET-1, but not ET-2 or ET-3, triggered a covert mesenteric vasodilator mechanism which was antagonized by bosentan. 3. Bosentan blocked all the effects of big ET-1, and, in a separate group of rats (n = 7), blocked all the haemodynamic effects of a lower dose of ET-1 (50 pmol kg-1), with the exception of a slight mesenteric vasoconstriction. 4. The most straightforward explanation of the results is that the major haemodynamic effects of ET-1, -2 and -3, and all the effects of big ET-1, are mediated through ETA- and/or ETB-receptors that are effectively antagonized by bosentan.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bosentan	Endothelin B receptor	Protein	Humans	Yes	Antagonist	Details
Sitaxentan	Endothelin B receptor	Protein	Humans	Unknown	Antagonist	Details