Characterization of contractile endothelin and angiotensin receptors in human resistance arteries: evidence for two endothelin and one angiotensin receptor.
Endothelin-1 (ET-1) and angiotensin II (AII) are potent vasoconstrictor hormones which regulate tissue perfusion and blood pressure. We pharmacologically characterized endothelin and angiotensin receptors mediating contractions of human mammary resistance arteries in myographs for isometric tension recording. ET-1 caused potent contractions. The concentration response curve was shifted to the right by ETA antagonist FR 139317, but a high sensitivity, low efficacy component remained. After incubation with ETB agonist sarafotoxin (S6c) this component of the concentration response curve resistant to FR 139317 disappeared. The ETA/ETB-receptor antagonist bosentan shifted the entire concentration response curve to the right. AI and AII caused marked contractions. The effects of AI were reduced by the ACE inhibitor benazeprilat, while those of AII were prevented by valsartan, an AT1 antagonist. In summary, in human resistance arteries, contractions to ET-1 are mediated by ETA- and ETB-receptors while those to AII are exclusively mediated by AT1-receptors.
Department of Research, University Hospital Basel, Switzerland.
M R
MR
Tschudi
T F
TF
Lüscher
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008323:Mammary Arteries / Q000737:chemistry*; D009119:Muscle Contraction / Q000187:drug effects; D010957:Plasmids; D011945:Receptors, Angiotensin / Q000032:analysis*; D017466:Receptors, Endothelin / Q000032:analysis*; D013449:Sulfonamides / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001381:Azepines; D001552:Benzazepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D011945:Receptors, Angiotensin; D017466:Receptors, Endothelin; D013449:Sulfonamides; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D000804:Angiotensin II; C079574:FR 139317; D000068756:Valsartan; D000803:Angiotensin I; D014633:Valine; C052133:benazeprilat; D000077300:Bosentan