Korean J Physiol Pharmacol.  2010 Aug;14(4):223-228. 10.4196/kjpp.2010.14.4.223.

Changes in Endothelin Receptor Type B and Neuronal Nitric Oxide Synthase in Puromycin Aminonucleoside-Induced Nephrotic Syndrome

• Bae EH
• Kim SW

• KMID: 2285406
• DOI: http://doi.org/10.4196/kjpp.2010.14.4.223

Abstract

The collecting duct endothelin (ET) system, which involves ET-1 and its two receptors, may play a role in the regulation of renal sodium in association with the nitric oxide synthase (NOS) system. We determined whether sodium retention is associated with changes in the endothelin and NOS systems at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndromes. On day 7 after puromycin aminonucleoside (PAN) injection, urinary sodium excretion was decreased, ascites had developed, and there was a positive sodium balance. ET-1 mRNA expression was increased in the inner medulla of the kidney, whereas protein expression of ET receptor type B (ET(B)R) was unchanged. The expression of neuronal NOS (nNOS) was decreased in the inner medulla. On day 14, urinary sodium excretion was unchanged compared with controls. The expression of ET(B)R increased, while nNOS expression in the inner medulla was comparable to controls. These findings suggest that decreased nNOS plays a role in the development of sodium retention in the nephrotic syndrome. Recovery of nNOS and increased renal ET(B)R synthesis may promote sodium excretion in later stages of the nephrotic syndrome (on day 14).

Keyword

Nephrotic syndrome; Endothelin receptor type B; Nitric oxide synthase; Puromycin aminonucleoside

MeSH Terms

Ascites
Endothelins
Kidney
Nephrotic Syndrome
Neurons
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Puromycin
Puromycin Aminonucleoside
Receptors, Endothelin
Retention (Psychology)
RNA, Messenger
Sodium
Endothelins
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Puromycin
Puromycin Aminonucleoside
RNA, Messenger
Receptors, Endothelin
Sodium

Figure

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  Fig. 1. The expression of ET-1, ETAR and ETBR mRNA in kidney. Fluorographs show ethidium bromide stained agarose gels containing reverse transcription-PCR products, and columns show real-time PCR data representing control and PAN-induced nephrotic syndrome groups (mean±SEM, n=8 each). ∗p<0.05 vs. control.

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  Fig. 2. The expression of ETBR in kidney. Immunoblotting data of ETBR in inner medulla was unchanged in PAN-treated rats compared with controls; it was increased on day 14 (mean±SEM, n=8 each). ∗p<0.05 vs. control.

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  Fig. 3. The expression of neuronal NOS in kidney. On day 7, nNOS protein expression was decreased. On day 14, nNOS protein expression was increased compared with controls (mean±SEM, n=8 each). ∗p<0.05 vs. control.

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  Fig. 4. Amount of urinary nitric oxide metabolite (NOx). Data are the mean±SEM of 8 rats for each group. ∗p<0.05 vs. control.

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