Expression of adrenomedullin 2/intermedin, a possible reno-protective peptide, is decreased in the kidneys of rats with hypertension or renal failure

Takuo Hirose, Kazuhito Totsune, Nobuyoshi Mori, Takefumi Mori, Ryo Morimoto, Hirohito Metoki, Kei Asayama, Masahiro Kikuya, Takayoshi Ohkubo, Masahiro Kohzuki, Kazuhiro Takahashi, Yutaka Imai

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Adrenomedullin 2/intermedin (AM2/IMD) is a potent vasodilator peptide with organ-protective effects and is abundantly expressed in the kidney. We examined the expression of AM2/IMD in the kidneys of rats with hypertension or chronic renal impairment using quantitative RT-PCR, radioimmunoassay, and immunohistochemistry. Kidneys of 8-wk-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were dissected into inner medulla, outer medulla, cortex, and glomerulus fractions. A rat renal impairment model was prepared by 5/6 nephrectomy in WKY rats. AM2/IMD mRNA levels were the highest in the cortex among four renal portions, and significantly lower in SHR than WKY rats in all renal portions. In the remnant kidneys of 5/6 nephrectomized rats, AM2/IMD mRNA levels were significantly decreased on days 3 and 56, whereas mRNA levels of calcitonin receptor-like receptor, receptor activity-modifying proteins-1 and -2, which form receptor for AM and AM2/IMD, were increased, compared with that in sham-operated rats. AM mRNA levels were decreased on day 3, but increased on day 56, after nephrectomy. Decreased immunoreactive AM2/IMD levels in the remnant kidneys of 5/6 nephrectomized rats on day 56 were confirmed by radioimmunoassay. The renal tubules were immunostained with anti-AM2/IMD antibody, with a decreased AM2/IMD immunostaining found in proximal tubular cells of 5/6 nephrectomized rats compared with sham-operated rats. In conclusion, intrarenal AM2/IMD expression is decreased in SHR and 5/6 nephrectomized rats. Given the organ-protective effects of AM2/IMD, the downregulation of AM2/IMD as an endogenous regulatory peptide may have a role in the progression of renal impairment.

Original languageEnglish
Pages (from-to)F128-F134
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number1
DOIs
Publication statusPublished - 2010 Jul 1

Keywords

  • Immunohistochemistry
  • Radioimmunoassay
  • Renal impairment
  • Reverse transcriptase polymerase chain reaction

ASJC Scopus subject areas

  • Physiology
  • Urology

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