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Time‐dependent up‐regulation of endothelin‐A receptors and down‐regulation of endothelin‐B receptors and nitric oxide synthase binding sites in the renal medulla of a rabbit model of partial bladder outlet obstruction: potential clinical relevance
Author(s) -
M. R. Khan,
Dashwood,
Wesley K. Thompson,
Faiz Mumtaz,
Mikhailidis,
Hiram Morgan
Publication year - 1999
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.1999.00320.x
Subject(s) - endocrinology , endothelin receptor , medicine , receptor , kidney , renal medulla , chemistry , nitric oxide synthase , renal cortex , nitric oxide , biology
Objective To assess the density of endothelin (ET) receptors (ET‐1 is a potent vasoconstrictor peptide acting on two known receptors, ET A and ET B ) and nitric oxide synthase (NOS) binding sites in the kidney of a rabbit model of bladder outlet obstruction (BOO). Materials and methods Partial BOO was created in adult New Zealand White rabbits; after 1, 3, 4 and 6 weeks of BOO, kidney sections were incubated with radioligands for ET‐1, ET A , ET B receptors and with [ 3 H]‐NOARG (a ligand for NOS). Autoradiographs were generated and analysed densitometrically. Sections were also assessed by NADPH histochemistry. Plasma creatinine, urea and electrolyte levels were regularly monitored. The control and 6‐week BOO kidneys were also evaluated ultrastructurally by electron microscopy. Results There was no significant change in plasma creatinine, urea and electrolyte levels. ET A and ET B receptor density was significantly greater in the medulla than in the cortex ( P <0.001) in all animals. There was an up‐regulation of ET A receptors ( P =0.03) and down‐regulation of ET B receptors ( P =0.03) and NOS binding sites ( P <0.001), as well as decreased NADPH staining in the medulla of 6‐week partial BOO kidneys. Electron microscopy detected glomerular disruption of the obstructed kidneys. Conclusion The time‐dependent changes in ET A and ET B receptors, NOS binding sites and NADPH staining in the renal medulla, as well as ultrastructural changes, occur despite normal renal function. These changes appear to be an early event and may play a role in the development of renal failure. Hence, the use of ET A receptor antagonists at this early stage may prevent the development of renal failure/impairment in BOO.