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Endothelial-derived vasoactive mediators in polycystic kidney disease
Muna A Al-Nimri1, Radko Komers, Terry T Oyama
1Division of Nephrology and Hypertension, Oregon Health and Science University, and Portland VA Medical Center, Portland, Oregon 97201, USA.
Kidney International
|April 5, 2003
Summary
Endothelial dysfunction, including increased endothelin-1 and impaired nitric oxide (NO) signaling, contributes to vasoconstriction and kidney function decline in autosomal dominant polycystic kidney disease (ADPKD) rat models.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Molecular Biology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is associated with hypertension and renal vasoconstriction.
- The specific mediators driving these hemodynamic changes in ADPKD are not fully understood, but endothelial-derived factors are implicated.
Purpose of the Study:
- To investigate the role of endothelial-derived mediators in the pathogenesis of hypertension and renal vasoconstriction in a rat model of polycystic kidney disease (PKD).
- To assess the impact of inhibiting the nitric oxide (NO) system on renal function and disease progression in cystic rats.
Main Methods:
- Male Han:SPRD rats with (cystic) and without (control) polycystic kidneys were treated with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, or vehicle.
- Measurements included blood pressure, proteinuria, urinary nitrite/nitrate excretion, inulin and para-aminohippurate (PAH) clearances.
- Renal protein levels of endothelin-1 (ET-1) and endothelial NOS (eNOS), as well as localization of eNOS and neuronal NOS (nNOS), were determined.
Main Results:
- L-NAME exacerbated hypertension and renal vasoconstriction in cystic rats but did not alter proteinuria or cyst growth.
- Cystic rats showed elevated renal ET-1 and eNOS levels.
- L-NAME altered eNOS distribution within renal cells and reduced its presence in vascular and glomerular structures, while nNOS was diminished.
Conclusions:
- Up-regulation of ET-1 and dysfunction of the NO system, characterized by altered eNOS localization, contribute to vasoconstriction in polycystic kidney disease (PKD).
- These endothelial-derived mediator alterations are likely involved in the progressive decline of renal function observed in PKD.