Published Online
on January 13, 2003

A more recent version of this article appeared on March 1, 2003

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Submitted on September 19, 2002
Revised on October 25, 2002

Angiotensin II-Mediated Negative Regulation of Npr1 Promoter Activity and Gene Transcription

Renu Garg and Kailash N. Pandey^*

From the Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center and School of Medicine, New Orleans, La.

^* To whom correspondence should be addressed. E-mail: kpandey{at}tulane.edu.

Abstract--Atrial natriuretic peptide receptor A (NPRA) plays important role(s) in the control of extracellular fluid volume and blood pressure homeostasis. We have determined and analyzed the functional promoter region of Npr1 gene (coding for NPRA) and studied the effect of angiotensin (Ang) II on its promoter activity and expression in cultured mouse mesangial cells. The promoter analysis of Npr1 gene revealed the presence of positive regulatory cis-elements in the regions -1982 to -1841 bp and -916 to -496 bp and of the repressor elements in the regions -1841 to -916 bp and 56 to 382 bp relative to transcription start site. The Ang II pretreatment of cultured mouse mesangial cells transiently transfected with the promoter construct pNPRA-luc1 significantly inhibited the promoter activity in a time- and dose-dependent manner, with a maximum inhibition at 24 hours. The Ang II-dependent repression of Npr1 promoter activity was partially blocked by both angiotensin type 1 and type 2 antagonists candesartan and PD 123,319, respectively. The mRNA level of NPRA was also downregulated by Ang II treatment as determined by semiquantitative reverse transcriptase-polymerase chain reaction assay. The deletion analysis showed that the promoter region 916 bp upstream of transcription start site contains the cis-elements involved in Ang II-mediated repression of transcription of Npr1 gene. The present study thus reveals the presence of functional cis-regulatory elements in the promoter region of the murine Npr1 gene and its transcriptional downregulation by vasoactive peptide Ang II.

Key words: natriuretic peptide receptor • angiotensin II • gene transcription • promoter analysis • gene expression • mesangial cells

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