Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia
Abstract Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2-year postpartum (PP), and...
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2021
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oai:doaj.org-article:7077ef83e8cd42cc88df1b001b63c30c2021-11-07T12:04:09ZAngiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia10.1186/s13293-021-00396-x2042-6410https://doaj.org/article/7077ef83e8cd42cc88df1b001b63c30c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13293-021-00396-xhttps://doaj.org/toc/2042-6410Abstract Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2-year postpartum (PP), and in the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of AT1-AA with a specific 7 amino acid peptide binding sequence (‘n7AAc’) improves pathophysiology observed in RUPP rats; however, the long-term effects of AT1-AA inhibition in PP is unknown. Pregnant Sprague Dawley rats were divided into three groups: normal pregnant (NP) (n = 16), RUPP (n = 15), and RUPP + ‘n7AAc’ (n = 16). Gestational day 14, RUPP surgery was performed and ‘n7AAc’ (144 μg/day) administered via osmotic minipump. At 10-week PP, mean arterial pressure (MAP), renal glomerular filtration rate (GFR) and cardiac functions, and cardiac mitochondria function were assessed. MAP was elevated PP in RUPP vs. NP (126 ± 4 vs. 116 ± 3 mmHg, p < 0.05), but was normalized in in RUPP + ‘n7AAc’ (109 ± 3 mmHg) vs. RUPP (p < 0.05). PP heart size was reduced by RUPP + ’n7AAc’ vs. RUPP rats (p < 0.05). Complex IV protein abundance and enzymatic activity, along with glutamate/malate-driven respiration (complexes I, III, and IV), were reduced in the heart of RUPP vs. NP rats which was prevented with ‘n7AAc’. AT1-AA inhibition during pregnancy not only improves blood pressure and pathophysiology of PE in rats during pregnancy, but also long-term changes in blood pressure, cardiac hypertrophy, and cardiac mitochondrial function PP.George W. BoozDaniel KennedyMichael BowlingTaprieka RobinsonDaniel AzubuikeBrandon FisherKaren BrooksPooja ChinthakuntlaNgoc H. HoangJonathan P. HoslerMark W. CunninghamBMCarticlePostpartumHypertensionCardiac mitochondrial functionCardiovascular diseasePreeclampsiaMedicineRPhysiologyQP1-981ENBiology of Sex Differences, Vol 12, Iss 1, Pp 1-12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Postpartum Hypertension Cardiac mitochondrial function Cardiovascular disease Preeclampsia Medicine R Physiology QP1-981 |
| spellingShingle |
Postpartum Hypertension Cardiac mitochondrial function Cardiovascular disease Preeclampsia Medicine R Physiology QP1-981 George W. Booz Daniel Kennedy Michael Bowling Taprieka Robinson Daniel Azubuike Brandon Fisher Karen Brooks Pooja Chinthakuntla Ngoc H. Hoang Jonathan P. Hosler Mark W. Cunningham Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia |
| description |
Abstract Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2-year postpartum (PP), and in the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of AT1-AA with a specific 7 amino acid peptide binding sequence (‘n7AAc’) improves pathophysiology observed in RUPP rats; however, the long-term effects of AT1-AA inhibition in PP is unknown. Pregnant Sprague Dawley rats were divided into three groups: normal pregnant (NP) (n = 16), RUPP (n = 15), and RUPP + ‘n7AAc’ (n = 16). Gestational day 14, RUPP surgery was performed and ‘n7AAc’ (144 μg/day) administered via osmotic minipump. At 10-week PP, mean arterial pressure (MAP), renal glomerular filtration rate (GFR) and cardiac functions, and cardiac mitochondria function were assessed. MAP was elevated PP in RUPP vs. NP (126 ± 4 vs. 116 ± 3 mmHg, p < 0.05), but was normalized in in RUPP + ‘n7AAc’ (109 ± 3 mmHg) vs. RUPP (p < 0.05). PP heart size was reduced by RUPP + ’n7AAc’ vs. RUPP rats (p < 0.05). Complex IV protein abundance and enzymatic activity, along with glutamate/malate-driven respiration (complexes I, III, and IV), were reduced in the heart of RUPP vs. NP rats which was prevented with ‘n7AAc’. AT1-AA inhibition during pregnancy not only improves blood pressure and pathophysiology of PE in rats during pregnancy, but also long-term changes in blood pressure, cardiac hypertrophy, and cardiac mitochondrial function PP. |
| format |
article |
| author |
George W. Booz Daniel Kennedy Michael Bowling Taprieka Robinson Daniel Azubuike Brandon Fisher Karen Brooks Pooja Chinthakuntla Ngoc H. Hoang Jonathan P. Hosler Mark W. Cunningham |
| author_facet |
George W. Booz Daniel Kennedy Michael Bowling Taprieka Robinson Daniel Azubuike Brandon Fisher Karen Brooks Pooja Chinthakuntla Ngoc H. Hoang Jonathan P. Hosler Mark W. Cunningham |
| author_sort |
George W. Booz |
| title |
Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia |
| title_short |
Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia |
| title_full |
Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia |
| title_fullStr |
Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia |
| title_full_unstemmed |
Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia |
| title_sort |
angiotensin ii type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/7077ef83e8cd42cc88df1b001b63c30c |
| work_keys_str_mv |
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| _version_ |
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