title: CD4+ T-helper cells stimulated in response to placental ischemia mediate hypertension during pregnancy.
abstract: We have shown that hypertension in response to chronic placental ischemia is associated with elevated inflammatory cytokines and CD4(+) T cells. However, it is unknown whether these cells play an important role in mediating hypertension in response to placental ischemia. Therefore, we hypothesize that reduced uterine perfusion pressure (RUPP)-induced CD4(+) T cells increase blood pressure during pregnancy. To answer this question, CD4(+) T cells were isolated from spleens at day 19 of gestation from control normal pregnant (NP) and pregnant RUPP rats, cultured, and adjusted to 10(6) cells per 100 μL of saline for intraperitoneal injection into NP rats at day 13 of gestation. On day 18, in the experimental groups of rats, arterial catheters were inserted, and on day 19 mean arterial pressure was analyzed. Inflammatory cytokines and antiangiogenic factor soluble fms-like tyrosine kinase 1 were determined via ELISA. Mean arterial pressure increased from 104±2 mm Hg in NP rats to 124±2 mm Hg in RUPP rats (P<0.001) and to 118±1 mm Hg in rats receiving RUPP CD4(+) T cells (P<0.001). Circulating tumor necrosis factor-α and soluble fms-like tyrosine kinase 1 were elevated in recipients of RUPP CD4(+) T cells to levels similar to control RUPP rats. In contrast, virgin rats injected with NP or RUPP CD4(+) T cells exhibited no blood pressure changes compared with control virgin rats. Importantly, mean arterial pressure did not change in recipients of NP CD4(+) T cells (109±3 mm Hg). These data support the hypothesis that RUPP-induced CD4(+) T cells play an important role in the pathophysiology of hypertension in response to placental ischemia.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505, USA.
authors.forename: Kedra
authors.initials: K
authors.lastname: Wallace
authors.forename: Sarah
authors.initials: S
authors.lastname: Richards
authors.forename: Pushpinder
authors.initials: P
authors.lastname: Dhillon
authors.forename: Abram
authors.initials: A
authors.lastname: Weimer
authors.forename: Eva-stina
authors.initials: ES
authors.lastname: Edholm
authors.forename: Eva
authors.initials: E
authors.lastname: Bengten
authors.forename: Melanie
authors.initials: M
authors.lastname: Wilson
authors.forename: James N
authors.initials: JN
authors.lastname: Martin
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D046110:Hypertension, Pregnancy-Induced / Q000276:immunology* / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D007511:Ischemia / Q000276:immunology* / Q000503:physiopathology; D010920:Placenta / Q000098:blood supply / Q000276:immunology* / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000503:physiopathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology
chemical_list: D016207:Cytokines; D040281:Vascular Endothelial Growth Factor Receptor-1