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

35 Citations (Scopus)

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

Fingerprint

Polycystic Kidney Diseases
Kidney
NG-Nitroarginine Methyl Ester
Endothelin-1
Vasoconstriction
Renal Hypertension
Proteinuria
Nitric Oxide
Autosomal Dominant Polycystic Kidney
Inulin
Nitric Oxide Synthase Type III
Nitrites
Nitric Oxide Synthase
Nitrates
Cytosol
Blood Vessels
Up-Regulation
Hemodynamics
Immunohistochemistry
Blood Pressure

Keywords

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

ASJC Scopus subject areas

  • Nephrology

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

Endothelial-derived vasoactive mediators in polycystic kidney disease. / Alnimri, Muna A; Komers, Radko; Oyama, Terry T.; Subramanya, Arohan R.; Lindsley, Jessie N.; Anderson, Sharon.

In: Kidney International, Vol. 63, No. 5, 01.05.2003, p. 1776-1784.

Research output: Contribution to journalArticle

Alnimri, MA, Komers, R, Oyama, TT, Subramanya, AR, Lindsley, JN & Anderson, S 2003, 'Endothelial-derived vasoactive mediators in polycystic kidney disease', Kidney International, vol. 63, no. 5, pp. 1776-1784. https://doi.org/10.1046/j.1523-1755.2003.00913.x
Alnimri, Muna A ; Komers, Radko ; Oyama, Terry T. ; Subramanya, Arohan R. ; Lindsley, Jessie N. ; Anderson, Sharon. / Endothelial-derived vasoactive mediators in polycystic kidney disease. In: Kidney International. 2003 ; Vol. 63, No. 5. pp. 1776-1784.
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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).",
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AU - Alnimri, Muna A

AU - Komers, Radko

AU - Oyama, Terry T.

AU - Subramanya, Arohan R.

AU - Lindsley, Jessie N.

AU - Anderson, Sharon

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N2 - 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).

AB - 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).

KW - Cystic disease

KW - Endothelin

KW - Glomerular filtration rate

KW - Nitric oxide

KW - Polycystic kidney

KW - Proteinuria

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