Renal cortex neuronal nitric oxide synthase in response to rapamycin in kidney transplantation

You Lin Tain, V. Müller, Attila J. Szabo, Aaron Erdely, Cheryl Smith, Chris Baylis

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Decreased renal neuronal nitric oxide synthase (nNOS) is present in various chronic kidney diseases although there is relative little known in chronic allograft nephropathy (CAN). Female sex increases the risk of acute rejection and calcineurin-inhibitor toxicity but decreases the risk of CAN. Rapamycin (RAPA) is an alternative immunosuppress although there is no information whether it is effective in females. We therefore investigated the efficacy of RAPA in both sexes and the impact of RAPA on renal cortex structure and nNOS expression. Male (M) and female (F) F344 kidneys were transplanted into same sex Lewis (ALLO) or F344 (ISO) recipients and treated with 1.6 mg/kg/day of RAPA for 10 days. Grafts were removed for renal histology and endothelial (e)NOS and neuronal (n)NOS protein measurements at 22 weeks. All ALLO rats survived without acute rejection. ALLO F survived with mild proteinuria and CAN at 22 weeks similar to ALLO M, while ISO F had better outcome than ISO M. Cortical nNOSα was undetectable in all RAPA groups; however, nNOSβ transcript and protein were compensatory increased. Both ALLO and ISO F showed higher medullary nNOSα but lower cortical eNOS abundance than M groups. In male ALLO RAPA decreased renal cortical nNOSα but increased nNOSβ expression. This may represent compensatory upregulation of nNOSβ when nNOSα-derived NO is deficient.

Original languageEnglish
Pages (from-to)80-86
Number of pages7
JournalNitric Oxide - Biology and Chemistry
Volume18
Issue number1
DOIs
Publication statusPublished - Feb 2008

Fingerprint

Nitric Oxide Synthase Type I
Sirolimus
Kidney Transplantation
Kidney
Allografts
Histology
Chronic Renal Insufficiency
Proteinuria
Grafts
Toxicity
Rats
Proteins
Up-Regulation
Transplants

Keywords

  • Chronic allograft nephropathy
  • Immunosuppression
  • Kidney transplant
  • Neuronal nitric oxide synthase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Renal cortex neuronal nitric oxide synthase in response to rapamycin in kidney transplantation. / Tain, You Lin; Müller, V.; Szabo, Attila J.; Erdely, Aaron; Smith, Cheryl; Baylis, Chris.

In: Nitric Oxide - Biology and Chemistry, Vol. 18, No. 1, 02.2008, p. 80-86.

Research output: Contribution to journalArticle

Tain, You Lin ; Müller, V. ; Szabo, Attila J. ; Erdely, Aaron ; Smith, Cheryl ; Baylis, Chris. / Renal cortex neuronal nitric oxide synthase in response to rapamycin in kidney transplantation. In: Nitric Oxide - Biology and Chemistry. 2008 ; Vol. 18, No. 1. pp. 80-86.
@article{632728d45ffc46e99cf6334a24864d80,
title = "Renal cortex neuronal nitric oxide synthase in response to rapamycin in kidney transplantation",
abstract = "Decreased renal neuronal nitric oxide synthase (nNOS) is present in various chronic kidney diseases although there is relative little known in chronic allograft nephropathy (CAN). Female sex increases the risk of acute rejection and calcineurin-inhibitor toxicity but decreases the risk of CAN. Rapamycin (RAPA) is an alternative immunosuppress although there is no information whether it is effective in females. We therefore investigated the efficacy of RAPA in both sexes and the impact of RAPA on renal cortex structure and nNOS expression. Male (M) and female (F) F344 kidneys were transplanted into same sex Lewis (ALLO) or F344 (ISO) recipients and treated with 1.6 mg/kg/day of RAPA for 10 days. Grafts were removed for renal histology and endothelial (e)NOS and neuronal (n)NOS protein measurements at 22 weeks. All ALLO rats survived without acute rejection. ALLO F survived with mild proteinuria and CAN at 22 weeks similar to ALLO M, while ISO F had better outcome than ISO M. Cortical nNOSα was undetectable in all RAPA groups; however, nNOSβ transcript and protein were compensatory increased. Both ALLO and ISO F showed higher medullary nNOSα but lower cortical eNOS abundance than M groups. In male ALLO RAPA decreased renal cortical nNOSα but increased nNOSβ expression. This may represent compensatory upregulation of nNOSβ when nNOSα-derived NO is deficient.",
keywords = "Chronic allograft nephropathy, Immunosuppression, Kidney transplant, Neuronal nitric oxide synthase",
author = "Tain, {You Lin} and V. M{\"u}ller and Szabo, {Attila J.} and Aaron Erdely and Cheryl Smith and Chris Baylis",
year = "2008",
month = "2",
doi = "10.1016/j.niox.2007.10.001",
language = "English",
volume = "18",
pages = "80--86",
journal = "Nitric Oxide - Biology and Chemistry",
issn = "1089-8603",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Renal cortex neuronal nitric oxide synthase in response to rapamycin in kidney transplantation

AU - Tain, You Lin

AU - Müller, V.

AU - Szabo, Attila J.

AU - Erdely, Aaron

AU - Smith, Cheryl

AU - Baylis, Chris

PY - 2008/2

Y1 - 2008/2

N2 - Decreased renal neuronal nitric oxide synthase (nNOS) is present in various chronic kidney diseases although there is relative little known in chronic allograft nephropathy (CAN). Female sex increases the risk of acute rejection and calcineurin-inhibitor toxicity but decreases the risk of CAN. Rapamycin (RAPA) is an alternative immunosuppress although there is no information whether it is effective in females. We therefore investigated the efficacy of RAPA in both sexes and the impact of RAPA on renal cortex structure and nNOS expression. Male (M) and female (F) F344 kidneys were transplanted into same sex Lewis (ALLO) or F344 (ISO) recipients and treated with 1.6 mg/kg/day of RAPA for 10 days. Grafts were removed for renal histology and endothelial (e)NOS and neuronal (n)NOS protein measurements at 22 weeks. All ALLO rats survived without acute rejection. ALLO F survived with mild proteinuria and CAN at 22 weeks similar to ALLO M, while ISO F had better outcome than ISO M. Cortical nNOSα was undetectable in all RAPA groups; however, nNOSβ transcript and protein were compensatory increased. Both ALLO and ISO F showed higher medullary nNOSα but lower cortical eNOS abundance than M groups. In male ALLO RAPA decreased renal cortical nNOSα but increased nNOSβ expression. This may represent compensatory upregulation of nNOSβ when nNOSα-derived NO is deficient.

AB - Decreased renal neuronal nitric oxide synthase (nNOS) is present in various chronic kidney diseases although there is relative little known in chronic allograft nephropathy (CAN). Female sex increases the risk of acute rejection and calcineurin-inhibitor toxicity but decreases the risk of CAN. Rapamycin (RAPA) is an alternative immunosuppress although there is no information whether it is effective in females. We therefore investigated the efficacy of RAPA in both sexes and the impact of RAPA on renal cortex structure and nNOS expression. Male (M) and female (F) F344 kidneys were transplanted into same sex Lewis (ALLO) or F344 (ISO) recipients and treated with 1.6 mg/kg/day of RAPA for 10 days. Grafts were removed for renal histology and endothelial (e)NOS and neuronal (n)NOS protein measurements at 22 weeks. All ALLO rats survived without acute rejection. ALLO F survived with mild proteinuria and CAN at 22 weeks similar to ALLO M, while ISO F had better outcome than ISO M. Cortical nNOSα was undetectable in all RAPA groups; however, nNOSβ transcript and protein were compensatory increased. Both ALLO and ISO F showed higher medullary nNOSα but lower cortical eNOS abundance than M groups. In male ALLO RAPA decreased renal cortical nNOSα but increased nNOSβ expression. This may represent compensatory upregulation of nNOSβ when nNOSα-derived NO is deficient.

KW - Chronic allograft nephropathy

KW - Immunosuppression

KW - Kidney transplant

KW - Neuronal nitric oxide synthase

UR - http://www.scopus.com/inward/record.url?scp=37349005509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37349005509&partnerID=8YFLogxK

U2 - 10.1016/j.niox.2007.10.001

DO - 10.1016/j.niox.2007.10.001

M3 - Article

VL - 18

SP - 80

EP - 86

JO - Nitric Oxide - Biology and Chemistry

JF - Nitric Oxide - Biology and Chemistry

SN - 1089-8603

IS - 1

ER -