Aminoguanidine attenuates hypertension, whereas 7-nitroindazole exacerbates kidney damage in spontaneously hypertensive rats: The role of nitric oxide

Chien Fu Huang, Chien Ning Hsu, Shao Ju Chien, Ying Jui Lin, Li Tung Huang, You Lin Tain*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

17 Scopus citations

Abstract

Nitric oxide (NO) deficiency contributes to hypertension and end-organ damage. Three nitric oxide synthase (NOS) isoforms have been identified: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). Whether selective nNOS or iNOS inhibition exacerbates kidney damage in spontaneously hypertensive rats (SHRs) remains unclear. Seven-week-old SHRs were randomly assigned to 4 groups (n=8 for each group): group 1, SHRs receiving no treatment; group 2 (SHR+7-NI), SHRs given7-nitroindazole (7-NI, nNOS inhibitor) in their drinking water (10 mg/kg/day); group 3 (SHR+salt), SHRs given 1% NaCl; and group 4 (SHR+AG), SHRs given0.1% aminoguanidine (AG; iNOS inhibitor) in drinking water. The mean arterial pressure of SHRs treated with salt was significantly elevated compared with untreated controls. While AG caused a decrease of mean arterial pressure at 8 and 12 weeks of age in SHRs, both 7-NI and salt exacerbated kidney injury. In addition, AG significantly increased l-arginine levels and the l-arginine-to-asymmetric dimethylarginine (ADMA) ratio in the kidney. Salt treatment decreased renal nNOS-α protein levels and reduced dimethylarginine dimethylaminohydrolase (DDAH) activity. Salt and AG treatment increased nNOS-β and l-citrulline levels in SHR kidneys. AG attenuates hypertension development by upregulation of l-citrulline-to- l-arginine conversion and an increase in the l-arginine-to-ADMA ratio in SHR kidneys. 7-NI impairs renal function but has no effect on blood pressure, suggesting reno-protective role for the nNOS. Salt exacerbates kidney damage mainly through decreasing renal nNOS-α protein levels and DDAH activity. Our findings highlight the protective role of the nNOS/NO pathway in the development of kidney damage in SHRs.

Original languageEnglish
Pages (from-to)233-240
Number of pages8
JournalEuropean Journal of Pharmacology
Volume699
Issue number1-3
DOIs
StatePublished - 15 01 2013

Keywords

  • Asymmetric dimethylarginine
  • Hypertension
  • Kidney injury
  • Neuronal nitric oxide synthase
  • Nitric oxide

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