Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes

Radko Komers, Jessie N. Lindsley, Terry T. Oyama, William E. Schutzer, John F. Reed, Scott L. Mader, Sharon Anderson

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of individual COX isoenzymes in diabetic nephropathy remains unknown. We explored COX-1 and COX-2 expression and hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or the COX-2 inhibitor NS398 in moderately hyperglycemic, streptozotocin-diabetic (D) and control (C) rats. Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control. Acute systemic administration of NS398 induced no significant changes in mean arterial pressure and renal plasma flow in either C or D rats but reduced glomerular filtration rate in D rats, resulting in a decrease in filtration fraction. VS had no effect on renal hemodynamics in D rats. Both inhibitors decreased urinary excretion of PGE2. However, only NS398 reduced excretion of thromboxane A2. In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic changes in diabetes.

Original languageEnglish (US)
Pages (from-to)889-898
Number of pages10
JournalJournal of Clinical Investigation
Volume107
Issue number7
StatePublished - 2001

Fingerprint

Cyclooxygenase 2
Kidney
Hemodynamics
Cyclooxygenase 1
Salicylates
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Renal Plasma Flow
Dilatation and Curettage
Thromboxane A2
Cyclooxygenase Inhibitors
Cyclooxygenase 2 Inhibitors
Diabetic Nephropathies
Streptozocin
Glomerular Filtration Rate
Dinoprostone
Isoenzymes
Diabetes Mellitus
Arterial Pressure
Enzymes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Komers, R., Lindsley, J. N., Oyama, T. T., Schutzer, W. E., Reed, J. F., Mader, S. L., & Anderson, S. (2001). Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes. Journal of Clinical Investigation, 107(7), 889-898.

Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes. / Komers, Radko; Lindsley, Jessie N.; Oyama, Terry T.; Schutzer, William E.; Reed, John F.; Mader, Scott L.; Anderson, Sharon.

In: Journal of Clinical Investigation, Vol. 107, No. 7, 2001, p. 889-898.

Research output: Contribution to journalArticle

Komers, R, Lindsley, JN, Oyama, TT, Schutzer, WE, Reed, JF, Mader, SL & Anderson, S 2001, 'Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes', Journal of Clinical Investigation, vol. 107, no. 7, pp. 889-898.
Komers R, Lindsley JN, Oyama TT, Schutzer WE, Reed JF, Mader SL et al. Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes. Journal of Clinical Investigation. 2001;107(7):889-898.
Komers, Radko ; Lindsley, Jessie N. ; Oyama, Terry T. ; Schutzer, William E. ; Reed, John F. ; Mader, Scott L. ; Anderson, Sharon. / Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes. In: Journal of Clinical Investigation. 2001 ; Vol. 107, No. 7. pp. 889-898.
@article{e498b93b4b434d0597701f0e4f90dcde,
title = "Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes",
abstract = "Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of individual COX isoenzymes in diabetic nephropathy remains unknown. We explored COX-1 and COX-2 expression and hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or the COX-2 inhibitor NS398 in moderately hyperglycemic, streptozotocin-diabetic (D) and control (C) rats. Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control. Acute systemic administration of NS398 induced no significant changes in mean arterial pressure and renal plasma flow in either C or D rats but reduced glomerular filtration rate in D rats, resulting in a decrease in filtration fraction. VS had no effect on renal hemodynamics in D rats. Both inhibitors decreased urinary excretion of PGE2. However, only NS398 reduced excretion of thromboxane A2. In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic changes in diabetes.",
author = "Radko Komers and Lindsley, {Jessie N.} and Oyama, {Terry T.} and Schutzer, {William E.} and Reed, {John F.} and Mader, {Scott L.} and Sharon Anderson",
year = "2001",
language = "English (US)",
volume = "107",
pages = "889--898",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "7",

}

TY - JOUR

T1 - Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes

AU - Komers, Radko

AU - Lindsley, Jessie N.

AU - Oyama, Terry T.

AU - Schutzer, William E.

AU - Reed, John F.

AU - Mader, Scott L.

AU - Anderson, Sharon

PY - 2001

Y1 - 2001

N2 - Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of individual COX isoenzymes in diabetic nephropathy remains unknown. We explored COX-1 and COX-2 expression and hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or the COX-2 inhibitor NS398 in moderately hyperglycemic, streptozotocin-diabetic (D) and control (C) rats. Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control. Acute systemic administration of NS398 induced no significant changes in mean arterial pressure and renal plasma flow in either C or D rats but reduced glomerular filtration rate in D rats, resulting in a decrease in filtration fraction. VS had no effect on renal hemodynamics in D rats. Both inhibitors decreased urinary excretion of PGE2. However, only NS398 reduced excretion of thromboxane A2. In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic changes in diabetes.

AB - Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of individual COX isoenzymes in diabetic nephropathy remains unknown. We explored COX-1 and COX-2 expression and hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or the COX-2 inhibitor NS398 in moderately hyperglycemic, streptozotocin-diabetic (D) and control (C) rats. Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control. Acute systemic administration of NS398 induced no significant changes in mean arterial pressure and renal plasma flow in either C or D rats but reduced glomerular filtration rate in D rats, resulting in a decrease in filtration fraction. VS had no effect on renal hemodynamics in D rats. Both inhibitors decreased urinary excretion of PGE2. However, only NS398 reduced excretion of thromboxane A2. In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic changes in diabetes.

UR - http://www.scopus.com/inward/record.url?scp=0035057565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035057565&partnerID=8YFLogxK

M3 - Article

VL - 107

SP - 889

EP - 898

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 7

ER -