Gestational hypertension in atrial natriuretic peptide knockout mice and the developmental origins of salt-sensitivity and cardiac hypertrophy

ANP +/−KO offspring exhibited normal BP at 14 weeks of age, but displayed significant CH (P < 0.001) as compared to ANP +/−WT offspring. ANP +/−KO offspring exhibited significantly increased gene expression of natriuretic peptide receptor A (NPR-A) (P < 0.001) and radioligand binding studies demonstrated significantly reduced NPR-C binding (P = 0.01) in the kidney. Treatment with high salt diet increased BP (P < 0.01) and caused LV hypertrophy (P < 0.001) and interstitial myocardial fibrosis only in ANP +/−WT and not ANP +/−KO offspring, suggesting gestational hypertension programs the offspring to show resistance to salt-induced hypertension and LV remodeling. Our data demonstrate that altered maternal environments can determine the salt-sensitive phenotype of offspring.