Document Detail


Alterations in circulatory and renal angiotensin-converting enzyme and angiotensin-converting enzyme 2 in fetal programmed hypertension.
MedLine Citation:
PMID:  19047579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Antenatal betamethasone treatment is a widely accepted therapy to accelerate lung development and improve survival in preterm infants. However, there are reports that infants who receive antenatal glucocorticoids exhibit higher systolic blood pressure in their early adolescent years. We have developed an experimental model of programming whereby the offspring of pregnant sheep administered clinically relevant doses of betamethasone exhibit elevated blood pressure. We tested the hypothesis as to whether alterations in angiotensin-converting enzyme (ACE), ACE2, and neprilysin in serum, urine, and proximal tubules are associated with this increase in mean arterial pressure. Male sheep were administered betamethasone (2 doses of 0.17 mg/kg, 24 hours apart) or vehicle at the 80th day of gestation and delivered at term. Sheep were instrumented at adulthood (1.8 years) for direct conscious recording of mean arterial pressure. Serum and urine were collected and proximal tubules isolated from the renal cortex. Betamethasone-treated animals had elevated mean arterial pressure (97+/-3 versus 83+/-2 mm Hg; P<0.05) and a 25% increase in serum ACE activity (48.4+/-7.0 versus 36.0+/-2.7 fmol/mL per minute) but a 40% reduction in serum ACE2 activity (18.8+/-1.2 versus 31.4+/-4.4 fmol/mL per minute). In isolated proximal tubules, ACE2 activity and expression were 50% lower in the treated sheep with no significant change in ACE or neprilysin activities. We conclude that antenatal steroid treatment results in the chronic alteration of ACE and ACE2 in the circulatory and tubular compartments, which may contribute to the higher blood pressure in this model of fetal programming-induced hypertension.
Authors:
Hossam A Shaltout; Jorge P Figueroa; James C Rose; Debra I Diz; Mark C Chappell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-12-01
Journal Detail:
Title:  Hypertension     Volume:  53     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-23     Completed Date:  2009-02-13     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  404-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Angiotensin I / metabolism
Angiotensin II / metabolism
Animals
Betamethasone / adverse effects,  pharmacology
Blood Pressure / drug effects,  physiology
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Fetal Development*
Glucocorticoids / adverse effects,  pharmacology
Hypertension / chemically induced,  metabolism*,  physiopathology
Kidney Tubules, Proximal / metabolism*
Male
Neprilysin / metabolism
Peptide Fragments / metabolism
Peptidyl-Dipeptidase A / metabolism*
Pregnancy
Sheep
Grant Support
ID/Acronym/Agency:
HD-17644/HD/NICHD NIH HHS; HD-47584/HD/NICHD NIH HHS; HL-51952/HL/NHLBI NIH HHS; HL-56973/HL/NHLBI NIH HHS; P01 HD047584/HD/NICHD NIH HHS; P01 HD047584-04/HD/NICHD NIH HHS; P01 HL051952/HL/NHLBI NIH HHS; P01 HL051952-150007/HL/NHLBI NIH HHS; R01 HD017644/HD/NICHD NIH HHS; R01 HD017644-23/HD/NICHD NIH HHS; R01 HD017644-25/HD/NICHD NIH HHS; R01 HL056973/HL/NHLBI NIH HHS; R01 HL056973-09/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Glucocorticoids; 0/Peptide Fragments; 0/angiotensin I (1-7); 11128-99-7/Angiotensin II; 9041-90-1/Angiotensin I; 9842X06Q6M/Betamethasone; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2; EC 3.4.24.11/Neprilysin
Comments/Corrections

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