Tissue-specific regulation of renal and cardiac atrial natriuretic factor gene expression in deoxycorticosterone acetate-salt rats

Hypertension. 1997 Dec;30(6):1342-7. doi: 10.1161/01.hyp.30.6.1342.

Abstract

Atrial natriuretic factor (ANF) is expressed in several noncardiac tissues where it may have an autocrine or paracrine function. Such function may be expected of locally synthesized ANF in the renal parenchyma. Previous investigations of the existence of ANF mRNA in the renal parenchyma have yielded conflicting results. The investigations reported here were designed to detect and measure ANF mRNA in normal rats and in rats subjected to a deoxycorticosterone acetate (DOCA)-salt treatment schedule known to strongly activate cardiac ANF gene expression. The expression of the renal ANF gene was measured using a newly developed quantitative competitive reverse transcription-polymerase chain reaction (QC-RT-PCR). This method uses an internal competitor that serves as an internal standard and makes the procedure independent of measurement relative to housekeeping genes. It was found that renal ANF mRNA levels were 10(7) times lower than those found in left or right atria, but immunoreactive (ir) renal ANF concentration by specific radioimmunoassay was 10(4) times lower than that of atrial irANF levels. Reverse-phase high-performance liquid chromatography analysis revealed that more than 99% of renal irANF is processed ANF(99-126). This finding suggests that most of the irANF measured in kidney extracts likely originates from atrial sources. Left atrial ANF mRNA levels after 1 week of DOCA-salt treatment was significantly higher than that of control rats ([21.06+/-2.99] x 10(-l5) mol/microg total RNAversus [8.59 +/-1.26] x 10(-5) mol/microg total RNA, P<.05). However, renal ANF mRNA levels in DOCA-salt rats were significantly decreased compared with those of control rats ([1.64+/-0.34] x 10(-22) mol/microg total RNA versus [3.96+/-0.61]x 10(-22) mol/microg total RNA, P<.05). These results indicate that (1) renal ANF mRNA can be consistently and specifically demonstrated after reverse transcription and PCR amplification; (2) renal and cardiac ANF synthesis are regulated in a tissue-specific, opposite manner during DOCA-salt treatment; and (3) the finding that renal ANF mRNA is downregulated by DOCA-salt treatment together with previous findings suggest the need for further investigation into the role of renal ANF mRNA downregulation in the pathogenetic mechanism that leads to volume expansion and hypertension after chronic DOCA-salt treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / biosynthesis*
  • Atrial Natriuretic Factor / blood
  • Desoxycorticosterone
  • Gene Expression Regulation*
  • Hypertension / chemically induced
  • Hypertension / metabolism*
  • Kidney / metabolism*
  • Male
  • Myocardium / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic*

Substances

  • RNA, Messenger
  • Desoxycorticosterone
  • Atrial Natriuretic Factor