Article date: July 1994
By: S.M. Gardiner, P.A. Kemp, J.E. March, T. Bennett, in Volume 112, Issue 3, pages 823-830
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).
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.
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.
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.
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).
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.
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.
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.
DOI: 10.1111/j.1476-5381.1994.tb13153.x
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