TISSUE-SPECIFIC REGULATION OF RENAL AND CARDIAC ATRIAL-NATRIURETIC-FACTOR GENE-EXPRESSION IN DEOXYCORTICOSTERONE ACETATE-SALT RATS

Citation
T. Ogawa et al., TISSUE-SPECIFIC REGULATION OF RENAL AND CARDIAC ATRIAL-NATRIURETIC-FACTOR GENE-EXPRESSION IN DEOXYCORTICOSTERONE ACETATE-SALT RATS, Hypertension, 30(6), 1997, pp. 1342-1347
Citations number
43
Journal title
ISSN journal
0194911X
Volume
30
Issue
6
Year of publication
1997
Pages
1342 - 1347
Database
ISI
SICI code
0194-911X(1997)30:6<1342:TRORAC>2.0.ZU;2-F
Abstract
Atrial natriuretic factor (ANF) is expressed in several noncardiac tis sues where it may have an autocrine or paracrine function. Such functi on may be expected of locally synthesized ANF in the renal parenchyma. Previous investigations of the existence of ANF mRNA in the renal par enchyma have yielded conflicting results. The investigations reported here were designed to detect and measure ANF mRNA in normal rats and i n rats subjected to a deoxycorticosterone acetate (DOCA)-salt treatmen t 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 react ion (QC-RT-PCR). This method uses an internal competitor that serves a s an internal standard and makes the procedure independent of measurem ent relative to housekeeping genes. It was found that renal ANF mRNA l evels were 10(7) times lower than those found in left or right atria, but immunoreactive (ir) renal ANF concentration by specific radioimmun oassay was 10(4) times lower than that of atrial irANF levels. Reverse -phase high-performance liquid chromatography analysis revealed that m ore than 99% of renal irANF is processed ANF(99-126). This finding sug gests that most of the irANF measured in kidney extracts likely origin ates 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]x10(-15) mol/mu g total RNA versus [8.59+/-1.26]x10(-1 5) mol/mu g 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]x10(-22) mol/mu g total RNA versus [3.96+/-0.61]x10 (-22) mol/mu g total RNA, P<.05). These results indicate that (1) rena l ANF mRNA can be consistently and specifically demonstrated after rev erse transcription and PCR amplification; (2) renal and cardiac ANF sy nthesis are regulated in a tissue-specific, opposite manner during DOC A-salt treatment; and (3) the finding that renal ANF mRNA is downregul ated by DOCA-salt treatment together with previous findings suggest th e need for further investigation into the role of renal ANF mRNA downr egulation in the pathogenetic mechanism that leads to volume expansion and hypertension after chronic DOCA-salt treatment.