774: AT1-AA enhances renal sensitivity and blood pressure in response to ANGII during pregnancy

Abstract

pressure in response to ANGII during pregnancy Justin Brewer, Ruisheng Liu, Kedra Wallace, Florian Herse, Janae Moseley, Ralf Dechend, Gerd Walluk, James Martin, Babbette LaMarca University of Mississippi Medical Center, Maternal Fetal Medicine, Jackson, MS, University of Mississippi Medical Center, Department of Physiology, Jackson, MS, University of Mississippi Medical Center, Obstetrics and Gynecology, Jackson, MS, HELIOS Clinic, Max-DelbruckCenter for Molecular Medicine, Berlin, Germany OBJECTIVE: Agonistic autoantibodies to the angiotensin II (ANGII) type I receptor (AT1-AA) are proposed to be important links between hypertension and increased maternal vascular sensitivity to ANGII during preeclampsia. This study was designed to determine effects of AT1-AA to enhance blood pressure (MAP) and renal vascular sensitivity to ANGII. STUDY DESIGN: First, we examined acute administration of ANGII on MAP in AT1-AA induced hypertensive pregnant rats. ANGII (100ng/ kg/min) was administered via jugular infusion to normal pregnant (NP) (n 6) controls and AT1-AA (1:50, n 10) infused pregnant rats. We examined the direct effects of ANGII on renal vasoconstriction in the presence and absence of the AT1-AA on isolated afferent arterioles (Af-Art) from NP rats. A dose response of increased constriction of the Af-Art with ANGII alone (10-11-10-8) or increasing AT1-AA alone (1:200, 1:150, and 1:100) was established. We subsequently measured Af-Art constriction to ANGII (10-11, 10-10, 10-9) with nonconstrictor dose of AT1-AA (1:200). Second, we examined chronic ANGII on MAP and renal artery resistive index (RI) in AT1-AA induced hypertensive pregnant rats. Power Doppler velocimetry was performed, bilaterally at two levels, using Vevo 770 unit with 30 Hz transducer and insonating angle 30. Statistical analysis was performed using STATA. RESULTS: MAP increased 30mmHg with acute ANGII in NP rats but markedly increased 47mmHg with ANGII in AT1-AA infused rats. Increasing ANGII from (10-11-10-8) decreased Af-Art diameter 1520% but sharply decreased Af-Art diameter 80% in AT1-AA pretreated vessels. MAP was 95 / 1 mmHg in NP and increased to 116 / 3 mmHg with chronic ANGII, to 120 / 3 mmHg with AT1-AA and was 112 / 3 mmHg, with ANGII AT1-AA (P 0.05). RI in the renal arteries was 0.67 in NP, 0.70 in AT1-AA infused pregnant rats, and was 0.74 (P 0.002) in ANGII AT1-AA pregnant rats. CONCLUSION: These data support the hypothesis that AT1-AA may be an important mechanism whereby MAP and renal vascular responses are greatly enhanced during preeclampsia.