Selective endothelin B receptor blockade does not influence BNP-induced natriuresis in man.
Brain natriuretic peptide (BNP) and endothelin-1 (ET-1) both exhibit natriuretic activity within the human kidney. Furthermore, they both act partly through activation of the endothelial nitric oxide pathway. Since ET-1 may cause vasodilation and natriuresis via stimulation of the ET-B receptor, the aim of the present study was to investigate whether renal ET-B receptors participate in the renal actions of BNP. In this placebo-controlled, crossover study, we infused BNP (4 pmol/kg/min) or placebo (i.v.) for 1 h, with or without co-infusion of the ET-B receptor antagonist BQ-788 (50 nmol/min) for 15 min on 4 separate days, in 10 healthy subjects (mean age 54+/-6 years.). During infusion, we measured effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) using PAH/inulin clearance. Cardiac output was measured before and after infusion, using echocardiography. Blood pressure and heart rate (HR) were monitored as well. Urine and plasma samples were taken every hour to measure diuresis, natriuresis, cyclic 3',5' guanosine monophosphate, and ET-1 levels. BNP with or without ET-B receptor blockade increased natriuresis and diuresis. In addition, BNP alone increased GFR and filtered load, without changing ERPF. BQ-788 infusion did not affect renal hemodynamics or natriuresis. Neither BNP nor BQ-788 altered cardiac output, blood pressure, and heart rate. In conclusion, the present study shows that selective ET-B receptor blockade has no effect on the BNP-induced natriuresis and glomerular filtration rate.
van der Zander
K
K
Department of Medicine, Cardiovascular Research Institute Maastricht (CARIM) and University Hospital Maastricht, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands.
Houben
A J H M
AJ
Webb
D J
DJ
Udo
E
E
Kietselaer
B
B
Hofstra
L
L
De Mey
J G R
JG
de Leeuw
P W
PW
D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004311:Double-Blind Method; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000652:urine; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology*; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology
D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D020097:Natriuretic Peptide, Brain; C086539:BQ 788; D006152:Cyclic GMP