Abstract 081: Intracerebroventricular (ICV) Infusion of Angiotensin-(1-7) Lowers Blood Pressure and Improves Autonomic Function in Antenatal Betamethasone Exposed Sheep
We have previously shown that antenatal betamethasone exposure in sheep is associated with a deficiency in angiotensin (Ang)-(1-7) levels in the cerebrospinal fluid of these betamethasone exposed (BMX) sheep and impaired baroreflex sensitivity for control of heart rate (BRS) by 6 weeks of age followed by persistent suppression of the reflex and elevation in mean blood pressure (MAP) by 6 months of age. In this study we sought to determine if supplementation of Ang-(1-7) administered via continuous infusion into the lateral ventricle of 4 month old BMX lambs (1-7, n=4) at a dose of 1.25ug/kg/hr for 1 week would improve the BRS, heart rate variability (HRV) and lower MAP and blood pressure variability (BPV). The control group received ICV artificial cerebrospinal fluid (aCSF, n=4). MAP and heart rate were recorded continuously via femoral arterial catheters and digitized before and one week after the ICV infusion. Both blood pressure and heart rate were analyzed to obtain measures of spontaneous BRS, HRV and BPV in the frequency and time domain. There were no differences in any of the measures between the two groups at baseline and no changes in the aCSF group after 1 week of ICV aCSF administration. Meanwhile, Ang-(1-7) ICV treatment significantly improved all measures of BRS compared to baseline, (HFa, 5.3±0.9 vs. 2.4±0.5 ms/mm Hg, p=0.03) and sequence ALL (6.5±1.6 vs. 1.9±0.9 ms/mm Hg, p=0.01). Ang-(1-7) also improved HRV measured as rMSSD (11.6±1.6 vs. 7±1.2 ms at baseline, p=0.04). Ang-(1-7) administration lowered MAP by 11.5 mm Hg (p < 0.05) compared to a rise of 2.0 mm Hg in the control group with no significant changes in heart rate or BPV in either group. These data support the hypothesis that Ang-(1-7) deficiency in the CSF contributes to the impaired autonomic function and reduced parasympathetic tone in betamethasone exposed sheep and replacement of the peptide in the brain will help restore these measures to normal levels. Elevating Ang-(1-7) levels in humans exposed antenatally to betamethasone may have beneficial cardiovascular effects.
Author Disclosures: M.J. Lawson: None. J.P. Figueroa: None. M.C. Chappell: None. D.I. Diz: None. H.A. Shaltout: None.
- © 2015 by American Heart Association, Inc.