title: Agonistic Autoantibodies to the Angiotensin II Type 1 Receptor Enhance Angiotensin II-Induced Renal Vascular Sensitivity and Reduce Renal Function During Pregnancy.
abstract: Preeclamptic women produce agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA) and exhibit increased blood pressure (mean arterial pressure), vascular sensitivity to angiotensin II (ANG II), and display a decrease in renal function. The objective of this study was to examine the renal hemodynamic changes during pregnancy in the presence of AT1-AAs with or without a slow pressor dose of ANG II. In this study, mean arterial pressure was elevated in all pregnant rats treated with ANG II with or without AT1-AA. Glomerular filtration rate was reduced from 1.90±0.16 mL/min in normal pregnant (NP) to 1.20±0.08 in ANG II+AT1-AA rats. Renal blood flow was decreased in ANG II+AT1-AA versus NP rats to 7.4±1.09 versus 15.4±1.75 mL/min. Renal vascular resistance was drastically increased between ANG II+AT1-AA versus NP rats (18.4±2.91 versus 6.4±0.77 mm Hg/mL per minute). Isoprostane excretion was increased by 3.5-fold in ANG II+AT1-AA versus NP (1160±321 versus 323±52 pg/mL). In conclusion, ANG II and AT1-AA together significantly decrease glomerular filtration rate by 37% and renal blood flow by 50% and caused a 3-fold increase in renal vascular resistance and isoprostane levels versus NP rats. These data indicate the importance of AT1-AAs to enhance ANG II-induced renal vasoconstriction and reduce renal function as mechanisms to cause hypertension as observed during preeclampsia.
authors.affiliation: From the Departments of Pharmacology and Toxicology (M.W.C., J.M.W., L.A., N.U., B.L.M.) and Obstetrics and Gynecology (B.L.M.), University of Mississippi Medical Center, Jackson; Experimental and Clinical Research Center, Charité Campus Buch, Max-Delbrück Center for Molecular Medicine, Berlin, Germany (G.W.); and Experimental and Clinical Research Center, HELIOS Clinic, Berlin, Germany (R.D.).
authors.forename: Mark W
authors.initials: MW
authors.lastname: Cunningham
authors.affiliation: From the Departments of Pharmacology and Toxicology (M.W.C., J.M.W., L.A., N.U., B.L.M.) and Obstetrics and Gynecology (B.L.M.), University of Mississippi Medical Center, Jackson; Experimental and Clinical Research Center, Charité Campus Buch, Max-Delbrück Center for Molecular Medicine, Berlin, Germany (G.W.); and Experimental and Clinical Research Center, HELIOS Clinic, Berlin, Germany (R.D.).
authors.forename: Jan M
authors.initials: JM
authors.lastname: Williams
authors.affiliation: From the Departments of Pharmacology and Toxicology (M.W.C., J.M.W., L.A., N.U., B.L.M.) and Obstetrics and Gynecology (B.L.M.), University of Mississippi Medical Center, Jackson; Experimental and Clinical Research Center, Charité Campus Buch, Max-Delbrück Center for Molecular Medicine, Berlin, Germany (G.W.); and Experimental and Clinical Research Center, HELIOS Clinic, Berlin, Germany (R.D.).
authors.forename: Lorena
authors.initials: L
authors.lastname: Amaral
authors.affiliation: From the Departments of Pharmacology and Toxicology (M.W.C., J.M.W., L.A., N.U., B.L.M.) and Obstetrics and Gynecology (B.L.M.), University of Mississippi Medical Center, Jackson; Experimental and Clinical Research Center, Charité Campus Buch, Max-Delbrück Center for Molecular Medicine, Berlin, Germany (G.W.); and Experimental and Clinical Research Center, HELIOS Clinic, Berlin, Germany (R.D.).
authors.forename: Nathan
authors.initials: N
authors.lastname: Usry
authors.affiliation: From the Departments of Pharmacology and Toxicology (M.W.C., J.M.W., L.A., N.U., B.L.M.) and Obstetrics and Gynecology (B.L.M.), University of Mississippi Medical Center, Jackson; Experimental and Clinical Research Center, Charité Campus Buch, Max-Delbrück Center for Molecular Medicine, Berlin, Germany (G.W.); and Experimental and Clinical Research Center, HELIOS Clinic, Berlin, Germany (R.D.).
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
authors.affiliation: From the Departments of Pharmacology and Toxicology (M.W.C., J.M.W., L.A., N.U., B.L.M.) and Obstetrics and Gynecology (B.L.M.), University of Mississippi Medical Center, Jackson; Experimental and Clinical Research Center, Charité Campus Buch, Max-Delbrück Center for Molecular Medicine, Berlin, Germany (G.W.); and Experimental and Clinical Research Center, HELIOS Clinic, Berlin, Germany (R.D.).
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: From the Departments of Pharmacology and Toxicology (M.W.C., J.M.W., L.A., N.U., B.L.M.) and Obstetrics and Gynecology (B.L.M.), University of Mississippi Medical Center, Jackson; Experimental and Clinical Research Center, Charité Campus Buch, Max-Delbrück Center for Molecular Medicine, Berlin, Germany (G.W.); and Experimental and Clinical Research Center, HELIOS Clinic, Berlin, Germany (R.D.). bblamarca@umc.edu.
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy / Q000276:immunology; D007677:Kidney Function Tests; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D021041:Placental Circulation / Q000187:drug effects / Q000276:immunology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000276:immunology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II
keywords: angiotensin II; autoantibodies; hypertension; preeclampsia; pregnancy