Distribution of endothelin receptor subtypes in the rat kidney. Renal and haemodynamic effects of the mixed (A/B) endothelin receptor antagonist bosentan.
The paracrine renal endothelin system has been implicated in acute and chronic kidney diseases. However, there are only few data about the expression of endothelin receptor subtypes and their impact on renal function in the normal rat kidney. Therefore, we analyzed the age-dependent expression of endothelin receptors (endothelin receptor A and B) using Scatchard analysis, in vitro and in vivo receptor autoradiography. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan on haemodynamic and renal function in conscious chronically instrumented rats. The renal endothelin receptor A and endothelin receptor B expression is age-dependent. The relative amount of endothelin receptor A significantly decreased with age, whereas the endothelin receptor B significantly increased with age. Compared to the other renal structures, a high endothelin receptor density (endothelin receptor B >> endothelin receptor A) was seen in the renal tubules and even more in the glomeruli. Bosentan blocks both the pressor and depressor response of endothelin. Blocking of both endothelin receptor subtypes using bosentan without application of endothelin, on the other hand, did not alter blood pressure, heart rate, renal blood flow, water excretion or glomerular filtration rate, but significantly decreased sodium excretion.
Abteilung für Nephrologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
B
B
Hocher
P
P
Rohmeiss
F
F
Diekmann
R
R
Zart
V
V
Vogt
S
S
Schiller
C
C
Bauer
K
K
Koppenhagen
A
A
Distler
N
N
Gretz
D000375:Aging; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011921:Rats, Inbred WKY; D017466:Receptors, Endothelin / Q000145:classification / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism / Q000652:urine; D013449:Sulfonamides / Q000494:pharmacology*; D014554:Urination / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D013449:Sulfonamides; C075771:BQ 3020; D012964:Sodium; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)