IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy
| Autor: | Florian Herse, James N. Martin, Babbette LaMarca, Ralf Dechend, Kedra Wallace, Pushpinder Dhillion, Judith Heath, Janae N Mosely, Gerd Wallukat, Jeremy Scott |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Physiology Placenta Blood Pressure Isoprostanes medicine.disease_cause Antioxidants Losartan Receptor Angiotensin Type 1 Autoimmunity Preeclampsia Cyclic N-Oxides Rats Sprague-Dawley Antibodies Monoclonal Murine-Derived Pregnancy Physiology (medical) Internal medicine Renin–angiotensin system medicine Animals Immunologic Factors B-Lymphocytes Chemistry Interleukin-17 Autoantibody Hypertension Pregnancy-Induced medicine.disease Angiotensin II Rats Oxidative Stress Endocrinology Call for Papers Pregnancy Animal Female Spin Labels Interleukin 17 Reactive Oxygen Species Rituximab Angiotensin II Type 1 Receptor Blockers Oxidative stress medicine.drug |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 303:R353-R358 |
| ISSN: | 1522-1490 0363-6119 |
| Popis: | Preeclampsia is associated with autoimmune cells TH17, secreting interleukin-17, autoantibodies activating the angiotensin II type I receptor (AT1-AA), and placental oxidative stress (ROS). The objective of our study was to determine whether chronic IL-17 increases blood pressure by stimulating ROS and AT1-AAs during pregnancy. To answer this question four groups of rats were examined: normal pregnant (NP, n = 20), NP+IL-17 ( n = 12), NP+tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine- N-oxyl) ( n = 7) (a superoxide dismutase mimetic that scavenges ROS), and NP+IL-17+tempol ( n = 11). IL-17 (150 pg/day) was infused into NP rats while tempol was administered via the drinking water ad libitum. On day 19 blood pressure (MAP) was recorded, and plasma, urine, and tissue were collected for isolation of ROS detected by chemilluminescent technique. Urinary isoprostane was measured by ELISA. AT1-AAs were determined via cardiomyocyte assay and expressed as beats per minute. MAP increased from 98 ± 3 mmHg in NP to 123 ± 3 mmHg in IL-17-infused NP rats. Urinary isoprostane increased from 1,029 ± 1 in NP to 3,526 ± 2 pg·mg−1·day−1 in IL-17-infused rats ( P < 0.05). Placental ROS was 436 ± 4 RLU·ml−1·min−1 ( n = 4) in NP and 702 ± 5 ( n = 5) RLU·ml−1·min−1 in IL-17-treated rats. Importantly, AT1-AA increased from 0.41 ± 0.05 beats/min in NP rats ( n = 8) to 18.4 ± 1 beats/min in IL-17 rats ( n = 12). Administration of tempol attenuated the hypertension (101 ± 3 mmHg) ROS (459 ± 5 RLU·ml−1·min−1) and blunted AT1-AAs (7.3 ± 0.6 beats/min) in NP+IL-17+tempol-treated rats. Additionally, AT1 receptor blockade inhibited IL-17-induced hypertension and placental oxidative stress. MAP was 105 ± 5 mmHg and ROS was 418 ± 5 RLU·ml−1·min−1 in NP+IL 17-treated with losartan. These data indicate that IL-17 causes placental oxidative stress, which serves as stimulus modulating AT1-AAs that may play an important role in mediating IL-17-induced hypertension during pregnancy. |
| Databáze: | OpenAIRE |
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