Urinary excretion of endothelin receptors ET A and ET B in hypertensive patients and normotensive subjects.
OBJECTIVE
Endothelin (ET)-1 is produced by most renal cell types. Renal tubular and vascular cells express both the ET receptors ET(A) and ET(B). Since significant amounts of ET-1 of renal origin were detected in human urine, urinary ET-1 has been used as an index for the capacity of renal ET-1 production. Here, we determine the existence of additional components of the intrarenal ET system, namely the ET(A) and ET(B) receptor subtypes, in the urine of normal and hypertensive subjects.


METHODS
ET(A) and ET(B) receptors were detected in urine samples that were concentrated by TCA precipitation, Speedvac or ProteoSpin.


RESULTS
Analysis of the human urine extracts revealed the existence of approximately 50 and 55 kDa of immunoreactive proteins, corresponding to ET(B) and ET(A), respectively, indicating that intact ET(A) and ET(B) are excreted in the urine of healthy subjects and hypertensive patients. Normotensive and hypertensive subjects had statistically comparable ET(B) excretion normalized to creatinine (0.58 +/- 0.16 vs. 0.83 +/- 0.17 microg/mg creatinine, respectively; p = 0.304). In contrast, ET(A) excretion was higher among hypertensive subjects (0.05 +/- 0.01 vs. 0.11 +/- 0.02 microg/mg creatinine; p = 0.0451). Immunostaining of ET(A) and ET(B) in the human urinary system revealed expression of both receptors, principally in tubular cells (mainly in medullary collecting ducts) and in the bladder urothelium, and ET(A) expression in the peritubular capillaries and arterioles. Urinary ET receptors closely and inversely correlated with indices of urine concentration, suggesting that their shedding is principally affected by urine flow.


CONCLUSIONS
ET receptors are present in human urine, conceivably originating within the urinary system. Their excretion is principally affected by urinary concentration. It remains to be determined whether urinary ET(A)/ET(B) is of physiological/pathophysiological relevance.
Karram
Tony
T
Department of Vascular Surgery, Rambam Medical Center, Technion, Haifa, Israel.
Khamaisi
Mogher
M
Bishara
Bishara
B
Ramadan
Rawi
R
Nitecki
Samy
S
Ben-Izhak
Ofer
O
Meretyk
Shimon
S
Winaver
Joseph
J
Heyman
Samuel N
SN
Hoffman
Aaron
A
Abassi
Zaid
Z
D015153:Blotting, Western; D003404:Creatinine / Q000652:urine; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D047468:Immunoprecipitation; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007672:Kidney Cortex / Q000473:pathology; D007679:Kidney Medulla / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014238:Trichloroacetic Acid / Q000737:chemistry
D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014238:Trichloroacetic Acid; D003404:Creatinine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases