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Loss of maternal atrial natriuretic peptide programs cardiac and renal gene expression: role of GATA4 and Npr‐1 in the fetal programming of cardiovascular health and disease
Author(s) -
Armstrong David WJ,
Tse M Yat,
Wong Philip G,
Pang Stephen C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.83.3
Subject(s) - atrial natriuretic peptide , offspring , medicine , endocrinology , natriuretic peptide , npr1 , fetus , pregnancy , biology , heart failure , genetics
Objective To determine the effect of loss of maternal atrial natriuretic peptide (ANP) on cardiac hypertrophy (CH) and salt‐sensitivity in offspring. Methods We obtained heterozygous offspring from ANP wild‐type (+/+) and knockout (−/−) dams (ANP+/− WT and ANP+/− KO offspring). Gene expression was measured using real‐time PCR. Results Maternal ANP had no effect on litter size or offspring growth. At 9‐weeks of age, ANP+/− KO had significantly higher left ventricular (LV) mass compared to ANP+/− WT . Left ventricular mRNA levels of ANP (a marker hypertrophy) and the pro‐hypertrophic factors GATA4 and P300 were significantly higher in ANP+/− KO mice. There was no significant difference in the hypertrophic response to daily injections of isoproterenol (ISO) between ANP+/− WT and ANP+/− KO , although CH remained significantly higher in ANP+/− KO . In the kidney of ANP+/− KO , we observed significantly higher mRNA levels of natriuretic peptide receptor 1 (Npr1), as well as P300 and Ets‐1, which are known to cooperatively stimulate Npr1 transcription. To determine the effect of elevated Npr1 on salt‐sensitivity, we treated offspring with a high salt diet for 5 weeks. Salt‐induced CH was only evident in ANP+/− WT and not ANP+/− KO mice. Conclusions Maternal ANP programs the structure and function of the cardio‐renal axis, and the loss of maternal ANP prevents salt‐sensitive CH in offspring, possibly via elevated renal Npr1. Grant Funding Source : Heart and Stroke Foundation of Ontario