Endothelin-1 causes systemic vasodilatation in anaesthetised turtles (Trachemys scripta) through activation of ETB-receptors.
The effects of endothelin-1 (ET-1) on systemic and pulmonary circulation were investigated in anaesthetised freshwater turtles (Trachemys scripta) instrumented with arterial catheters and blood flow probes. Bolus intra-arterial injections of ET-1 (0.4-400 pmol kg(-1)) caused a dose-dependent systemic vasodilatation that was associated with a decrease in systemic pressure (P(sys)) and a rise in systemic blood flow (Q(sys)), causing systemic conductance (G(sys)) to increase. ET-1 had no significant effects on the pulmonary vasculature, heart rate (fh) or total stroke volume (Vs(tot)). This response differs markedly from mammals, where ET-1 causes an initial vasodilatation that is followed by a pronounced pressor response. In mammals, the initial dilatation is caused by stimulation of ET(B)-receptors, while the subsequent constriction is mediated by ET(A)-receptors. In the turtles, infusion of the ET(B)-receptor agonist BQ-3020 (150 pmol kg(-1)) elicited haemodynamic changes that were similar to those of ET-1, and the effects of ET-1 were not affected by the ET(A)-antagonist BQ-610 (0.15 micromol kg(-1)). Conversely, all effects of ET-1 were virtually abolished after specific ET(B)-receptor blockade with the ET(B)-antagonist BQ-788 (0.15 micromol kg(-1)). The subsequent treatment with the general ET-receptor antagonist tezosentan (15.4 micromol kg(-1)) did not produce effects that differed from the treatment with ET(B)-antagonist, and the blockade of ET-1 responses persisted. This present study indicates, therefore, that ET(B)-receptors are responsible for the majority of the cardiovascular responses to ET-1 in Trachemys.
Skovgaard
Nini
N
Department of Zoophysiology, Institute of Biological Sciences, University of Aarhus, Denmark. nini.jensen@biology.au.dk
Warren
Daniel E
DE
Jackson
Donald C
DC
Wang
Tobias
T
D000704:Analysis of Variance; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism*; D013318:Stroke Volume; D013777:Tetrazoles / Q000494:pharmacology; D014426:Turtles / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D011725:Pyridines; D017466:Receptors, Endothelin; D013777:Tetrazoles; C087220:BQ 610; C075771:BQ 3020; C086539:BQ 788; C120582:tezosentan