Localization of endothelin ETA and ETB receptor-mediated constriction in the renal microcirculation of rats.
1. The aim of the study was to visualize endothelin-1 (ET-1)-mediated constriction in renal vessels of cortical and juxtamedullary glomeruli in the split hydronephrotic rat kidney in vivo and to functionally characterize the ET receptor subtypes involved. 2. ET-1 (10(-9) M) constricted preglomerular vessels (by 6-18%) and efferent arterioles (by 11-13%), and decreased glomerular blood flow (GBF, by 55%) of cortical and juxtamedullary glomeruli. 3. The ETA antagonist BQ-123 (10(-6) M), as well as the ETB antagonist BQ-788 (2 x 10(-7) M) and IRL 1038 (10(-6) M), shifted the concentration-response curve of GBF for ET-1 to the right by one order of magnitude. While BQ-123 antagonized ET-1 constriction only in preglomerular vessels, BQ-788 and IRL 1038 were effective both in preglomerular vessels and efferent arterioles. 4. The ETB agonist IRL 1620 (10(-8) M) reduced GBF by 50% and constricted efferent arterioles (by 20-33%) about two times more than preglomerular vessels (by 6-14%). 5. Our results suggest that in renal cortical and juxtamedullary vessels of rats, ET-1-induced preglomerular vasoconstriction is mediated by ETA and ETB receptors, while efferent vasoconstriction is predominantly mediated by ETB receptors, which might have important consequences for the regulation of glomerular filtration pressure by ET.
Endlich
K
K
Institut für Anatomie und Zellbiologie I der Universität Heidelberg, Germany.
Hoffend
J
J
Steinhausen
M
M
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008833:Microcirculation / Q000502:physiology*; D009401:Nephrosis / Q000378:metabolism / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C074308:sovateltide; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); C072247:cyclo(Trp-Asp-Pro-Val-Leu)