Background/Aims: Endothelin (ET)-1 is produced by most renal cell types. Renal tubular and vascular cells express both the ET receptors ETA and ETB. 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 ETA and ETB receptor subtypes, in the urine of normal and hypertensive subjects. Methods: ETA and ETB 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 ETB and ETA, respectively, indicating that intact ETA and ETB are excreted in the urine of healthy subjects and hypertensive patients. Normotensive and hypertensive subjects had statistically comparable ETB excretion normalized to creatinine (0.58 ± 0.16 vs. 0.83 ± 0.17 μg/mg creatinine, respectively; p = 0.304). In contrast, ETA excretion was higher among hypertensive subjects (0.05 ± 0.01 vs. 0.11 ± 0.02 μg/mg creatinine; p = 0.0451). Immunostaining of ETA and ETB 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 ETA 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. Conclusion: 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 ETA/ETB is of physiological/pathophysiological relevance.

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