Endothelin ETA and ETB receptors mediate vasoconstriction and prostanoid release in the isolated kidney of the rat.
Endothelin-1 or sarafotoxin 6c (10(-12) to 10(-9) M) induced concentration-dependent increases in perfusion pressure in the isolated perfused kidney of the rat, and increased the release of 6-keto-prostaglandin F1 alpha, prostaglandin E2 and prostaglandin F2 alpha. The pressor effects of endothelin-1 were partially antagonised by BQ-123 (10(-6) M) and more strongly so by the endothelin ETA/B receptor non-selective antagonist PD 145065 (10(-6) M). PD 145065, but not BQ-123, also completely blocked the pressor effects of sarafotoxin 6c. The releases of prostanoids induced by endothelin-1 were greatly reduced by infusion of either BQ-123 or PD 145065, whereas PD 145065, but not BQ-123, strongly antagonised the releases induced by sarafotoxin 6c. These results indicate that the vasoconstrictions and the prostanoid releases induced by the endothelin/sarafotoxin peptides are mediated by the activation of both endothelin ETA and endothelin ETB receptors in the isolated perfused kidney of the rat.
Warner
T D
TD
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Battistini
B
B
Allcock
G H
GH
Vane
J R
JR
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011453:Prostaglandins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C082887:PD 145065; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone; C072247:cyclo(Trp-Asp-Pro-Val-Leu)