Interaction between NO synthase and NADPH oxidase in control of sodium transport by the renal thick ascending limb during diabetes.
Acta Physiol (Oxf)
; 209(2): 148-55, 2013 Oct.
Article
en En
| MEDLINE
| ID: mdl-23841645
ABSTRACT
AIM:
During type 1 diabetes (T1D), the medullary thick ascending limb (mTAL) displays an NADPH oxidase-dependent increase in sodium transport, in concert with increased NO production by NO synthase 1 (NOS1) and NOS2. We hypothesized that NOS1- and/or NOS2-derived NO blunts T1D-induced activation of sodium transport in the mTAL.METHODS:
T1D was induced by streptozotocin injection (STZ rats); sham rats received vehicle. Three-to-four weeks later, mTAL were isolated from both groups for assay of nitrite and superoxide production, and O2 consumption in the absence or presence of various inhibitors.RESULTS:
Apocynin (NADPH oxidase inhibitor) normalized superoxide production and ouabain-sensitive O2 consumption and furosemide-sensitive O2 consumption by mTALs from STZ rats, without altering O2 consumption by mTALs from sham rats. Apocynin also unmasked a T1D-induced increase in nitrite production. NOS inhibition did not alter superoxide production in either group. In sham mTAL, total NOS inhibition, but not isoform-specific inhibition of NOS1 or NOS2, increased ouabain- and furosemide-sensitive O2 consumption, confirming a tonic inhibitory impact of NOS3 on sodium transport. In contrast, neither total nor isoform-specific NOS inhibition altered O2 consumption by STZ mTAL. Apocynin treatment of STZ mTAL unveiled the ability of isoform-specific NOS inhibition to significantly increase O2 consumption, without further increase in O2 consumption with total NOS inhibition.CONCLUSION:
Under normal conditions, NOS3-derived NO inhibits sodium transport in the mTAL. T1D dismantles the impact of NOS-mediated inhibition of sodium transport as a result of NADPH oxidase-dependent NO scavenging. Inhibition of NADPH oxidase to preserve NO bioavailability reveals an inhibitory impact of NOS1- and NOS2-derived NO on sodium transport in the mTAL.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sodio
/
Óxido Nítrico Sintasa
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NADPH Oxidasas
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Diabetes Mellitus Experimental
/
Nefronas
Límite:
Animals
Idioma:
En
Revista:
Acta Physiol (Oxf)
Asunto de la revista:
FISIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos