Document Detail


Differential effects of clinical doses of antenatal betamethasone on nephron endowment and glomerular filtration rate in adult sheep.
MedLine Citation:
PMID:  19897787     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Antenatal steroid administration is associated with alterations in fetal kidney development and hypertension. However, a causal relationship between nephron deficit and hypertension has not been established. In this study, we measured nephron number, renal function, and blood pressure in sheep exposed antenataly to betamethasone. Pregnant sheep were given 2 betamethasone doses (0.17 mg/kg) or vehicle at 80 and 81 days gestational age and allowed to deliver at term. Data were obtained from a fetal cohort and 2 adult cohorts and were analyzed by analysis of variance (ANOVA) and/or 2 sample t test. Antenatal betamethasone induced a 26% reduction in the number of nephrons in both males and females in the absence of intrauterine growth restriction and/or prematurity. Adult males presented a reduction in glomerular filtration rate (GFR; 132 +/- 12.7 vs 114 +/- 7.0 mL/min, P < .05). Betamethasone administration was also associated with an increase in arterial blood pressure of similar magnitude in male (mean arterial pressure [MAP] in mm Hg; 98 +/- 2.7 vs 105 +/- 2.4) and female (96 +/- 1.9 vs 105 +/- 2.4) adult sheep and the increase in blood pressure preceded the decrease in GFR in the males. Furthermore, we found no significant association between the magnitude of the decrease in nephron number and the magnitude of the increase in arterial blood pressure. Our data thus support the conclusion that exposure to glucocorticoids at a time of rapid kidney growth is associated with an elevation in blood pressure that does not appear related solely to the reduction in nephron number.
Authors:
Jie Zhang; G Angela Massmann; James C Rose; Jorge P Figueroa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-11-06
Journal Detail:
Title:  Reproductive sciences (Thousand Oaks, Calif.)     Volume:  17     ISSN:  1933-7205     ISO Abbreviation:  Reprod Sci     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-04     Completed Date:  2010-04-22     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  101291249     Medline TA:  Reprod Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  186-95     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Betamethasone / pharmacology*
Blood Pressure / drug effects
Dose-Response Relationship, Drug
Female
Gestational Age
Glomerular Filtration Rate / drug effects
Glucocorticoids / pharmacology*
Hypertension, Renal / chemically induced*,  pathology,  physiopathology
Inulin / diagnostic use
Kidney Function Tests
Male
Nephrons / abnormalities*,  pathology,  physiology
Pregnancy
Prenatal Exposure Delayed Effects / pathology*,  physiopathology
Sheep
p-Aminohippuric Acid / diagnostic use
Grant Support
ID/Acronym/Agency:
HL 68728/HL/NHLBI NIH HHS; P01HD04784/HD/NICHD NIH HHS; R01 HD017644/HD/NICHD NIH HHS; R01 HL068728/HL/NHLBI NIH HHS; R01 HL068728-07/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Glucocorticoids; 9005-80-5/Inulin; 9842X06Q6M/Betamethasone; Y79XT83BJ9/p-Aminohippuric Acid
Comments/Corrections

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