Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes

Radko Komers, Jessie N. Lindsley, Terry T. Oyama, Kristen M. Allison, Sharon Anderson

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Abstract

Nitric oxide (NO) has been implicated in the pathogenesis of renal hemodynamic changes in diabetes mellitus. However, the contribution of nitric oxide synthase (NOS) isoforms to intrarenal production of NO in diabetes remains unknown. To explore the role of NOS1 in the control of renal hemodynamics in diabetes, we assessed renal responses to inhibition of NOS1 with S-methyl-L-thiocitrulline (SMTC; administered into the abdominal aorta) in moderately hyperglycemic streptozotocin-diabetic rats (D) and their nondiabetic (C) and normoglycemic diabetic counterparts. The contribution of other NOS isoforms was also evaluated by assessing the responses to nonspecific NOS inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME)] in SMTC-treated diabetic rats. The number of NOS1-positive cells in macula densa of D and C kidneys was also evaluated by immunohistochemistry. D rats demonstrated elevated glomerular filtration rate (GFR) compared with C. SMTC (0.05 mg/kg) normalized GFR in D but had no effect in C. SMTC-induced reduction of renal plasma flow (RPF) was similar in C and D. Normoglycemic diabetic rats demonstrated blunted renal hemodynamic responses to NOS1 inhibition compared with hyperglycemic animals. Mean arterial pressure was stable in all groups. L-NAME induced a further decrease in RPF, but not in GFR, in D rats treated with SMTC. Immunohistochemistry revealed increased numbers of NOS1-positive cells in D. These observations suggest that NOS1-derived NO plays a major role in the pathogenesis of renal hemodynamic changes early in the course of diabetes. NOS1 appears to be the most important isoform in the generation of hemodynamically active NO in this condition.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume279
Issue number3 48-3
StatePublished - 2000

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Nitric Oxide Synthase Type I
Hemodynamics
Kidney
NG-Nitroarginine Methyl Ester
Nitric Oxide
Glomerular Filtration Rate
Nitric Oxide Synthase
Renal Plasma Flow
Protein Isoforms
Immunohistochemistry
Dilatation and Curettage
Abdominal Aorta
Streptozocin
Diabetes Mellitus
Arterial Pressure

Keywords

  • Diabetic nephropathy
  • Glomerular filtration rate
  • Immunohistochemistry
  • Kidney

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes. / Komers, Radko; Lindsley, Jessie N.; Oyama, Terry T.; Allison, Kristen M.; Anderson, Sharon.

In: American Journal of Physiology - Renal Physiology, Vol. 279, No. 3 48-3, 2000.

Research output: Contribution to journalArticle

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