Endothelial-derived vasoactive mediators in polycystic kidney disease

Muna A Alnimri, Radko Komers, Terry T. Oyama, Arohan R. Subramanya, Jessie N. Lindsley, Sharon Anderson

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Background. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by hypertension and renal vasoconstriction. Mediators of these hemodynamic changes are not well understood, but evidence suggests that endothelial-derived mediators may participate. Methods. Baseline measurements of blood pressure, proteinuria, and urinary nitrite/nitrate excretion were performed in control and cystic male Han:SPRD rats (6 weeks of age). They were then treated with the nitric oxide (NO), nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), or vehicle, for 6 weeks. After repeat systemic measurements, renal function was determined using inulin and para-aminohippurate (PAH) clearances. Levels of renal endothelin-1 (ET-1) and renal endothelial NOS (eNOS) proteins were determined, and immunohistochemistry localized renal eNOS and neuronal NOS (nNOS). Results. Administration of L-NAME aggravated systemic hypertension and renal vasoconstriction in the cystic rats, but did not affect the progression of proteinuria or cystic expansion. Cystic rats demonstrated marked increases in renal ET-1 and eNOS levels. L-NAME reduced eNOS expression in the membrane compartment, but increased eNOS in the cytosol. Localization studies indicated that renal eNOS was abundant in nonvascular compartments, but not in renal vascular and glomerular structures, whereas renal nNOS was diffusely diminished. Conclusion. These alterations of endothelial-derived mediators (up-regulation of ET-1, and dysfunction of the NO system) contribute to vasoconstriction, and thereby are likely to contribute to the progressive loss of renal function in polycystic kidney disease (PKD).

Original languageEnglish (US)
Pages (from-to)1776-1784
Number of pages9
JournalKidney International
Volume63
Issue number5
DOIs
StatePublished - May 1 2003
Externally publishedYes

Keywords

  • Cystic disease
  • Endothelin
  • Glomerular filtration rate
  • Nitric oxide
  • Polycystic kidney
  • Proteinuria

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Alnimri, M. A., Komers, R., Oyama, T. T., Subramanya, A. R., Lindsley, J. N., & Anderson, S. (2003). Endothelial-derived vasoactive mediators in polycystic kidney disease. Kidney International, 63(5), 1776-1784. https://doi.org/10.1046/j.1523-1755.2003.00913.x