Atrial Natriuretic peptide deficiency in hypertensive pregnant rats induces adverse cardiac remodeling, fetal outcomes and maternal vascular dysfunction

The Dahl Salt-Sensitive (DSS) rat is a well-established model of hypertensive pregnancy and develops spontaneous increases in blood pressure and proteinuria during gestation. Atrial natriuretic peptide (ANP), a hormone secreted by the right atrium in response to hypervolemia, is elevated in healthy pregnancy and clinical data suggests low ANP levels may induce adverse cardiac and vascular function. Although hypertensive pregnancies characteristically present with low ANP levels, whether ANP plays a role to protect cardiac and vascular function in hypertensive pregnancy is unknown. Therefore, we hypothesize that ANP deficiency in the DSS rat model of hypertensive pregnancy will result in pronounced vascular and cardiac dysfunction. We utilized transgenic DSS rats with ANP deficiency (DSS ANP KO) and wild-type (WT) Sprague Dawley rats at 12 weeks of age, which were mated with age- and strain-matched males to develop timed pregnancies. On gestation day (GD) 19, rats were anesthetized, and doppler ultrasound was performed to assess uterine resistance and cardiac function. On gestation day 20, animals were euthanized, and vascular function was assessed. Vascular data was collected using wire myography and analyzed by 2-W ANOVA w/RM. Pairwise comparisons were by student’s t-test. Although echocardiography did not reveal overt cardiac dysfunction (as assessed by ejection fraction, fractional shortening and other cardiac measures), DSS ANP KO rats exhibited significantly larger heart masses (.004±7.87e-005 heart/body wt DSS ANP KO vs.003±1.29e-3 WT, p<0.0001). UARI showed a trend towards increased resistance in DSS ANP KO rats (.708±.0155 [PSV-EDV]/PSV DSS ANP KO vs.588±.0688 WT, p=.072). Pups from DSS ANP KO rats were significantly smaller than those from WT rats (2.16±.025g DSS ANP KO vs 2.28±.034 WT, p<0.0054), and litter sizes were smaller (8.57±.78 pups/litter DSS ANP KO vs 11.8±1.07 WT, p=0.0313). Placental efficiency in DSS ANP KO rats was markedly reduced compared to WT rats (4.47±.084 pup wt/placenta ratio DSS ANP KO vs 5.01±.111 WT, p<0.0001). DSS ANP KO animals developed endothelial dysfunction at GD20, which was assessed through vascular relaxation in response to acetylcholine (p=.016 WT vs DSS ANP KO, concentration response 1nM-10µM). Collectively, these data indicate that ANP deficiency in hypertensive rats did not lead to overt cardiac dysfunction during pregnancy as assessed by doppler ultrasound; however, our findings indicate that the ANP deficiency in DSS rats demonstrates elevated vascular resistance and evidence of cardiac hypertrophy alongside adverse fetal reprogramming and growth restriction. NIH 1R01HL169576, R01HL148114, U54HL169191 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.