Characterisation of constrictor endothelin receptors in the human internal thoracic artery and saphenous vein.
We studied the endothelin receptors mediating contraction in the human saphenous vein (SV) and internal thoracic artery (ITA). In the SV, the ET(A)-receptor antagonist BQ123 (1 microM) did not significantly shift the ET-1 concentration-response curve but did cause a parallel shift in the ITA. In the SV, the ET(A)-receptor agonist sarafotoxin 6b (S6b) produced a monophasic concentration-response curve that was antagonised biphasically by BQ123 (0.1-1 microM). In the ITA, S6b was an ineffective agonist with contractions seen only at 3 x 10(-9) M upward. The ET(B)-receptor agonist sarafotoxin 6c (S6c) caused constrictions in only 74% of SV rings and 42% of ITA rings. In the tissues that did respond, S6c caused a monophasic concentration-response curve with a lower maximal response than ET-1. The ET(B) antagonist BQ788 did not antagonise the responses to ET-1 in either the SV or the ITA but did antagonise the responses to S6c in the SV. The results from this study suggest that mainly ET(A) receptors mediate the contractile responses in the human SV and ITA. There is also evidence for an ET(B)-mediated response, although the contractions were much smaller than those elicited by ET-1. We also conclude that the ET(A) receptors mediating responses in these human vessels are atypical because of the different effects of BQ123 on the two vessels.
Pate
M A
MA
Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Harefield Hospital, Middlesex, England.
Chester
A H
AH
Crabbe
D S
DS
Amrani
M
M
Brown
T J
TJ
Roach
A G
AG
Yacoub
M H
MH
D000328:Adult; D000368:Aged; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000494:pharmacology; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)