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Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and hypertension in the rat offspring.
- Source :
-
The Journal of physiology [J Physiol] 2007 Mar 01; Vol. 579 (Pt 2), pp. 503-13. Date of Electronic Publication: 2007 Jan 04. - Publication Year :
- 2007
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Abstract
- Maternal treatment with the synthetic glucocorticoid, dexamethasone has been reported to result in a nephron deficit and development of hypertension in the offspring of rats. However, it is not known whether elevated maternal corticosterone (CORT), the natural glucocorticoid, has similar effects on blood pressure and nephron endowment. The present study investigated the effects of CORT (0.8 mg kg(-1) day(-1)) administration on embryonic day 14 (E14) and E15 of pregnancy on: (1) nephron number at postnatal day 30 (PN30); (2) blood pressure at PN120; and (3) receptors of the renal renin-angiotensin system (RRAS) (AT(1)Ra, AT(1)Rb and AT(2)Ra) during both embryonic (E16, E20) and adolescent (PN30) life. Plasma CORT concentrations were approximately doubled 30 min after injection. Unbiased stereological analysis revealed that maternal CORT treatment resulted in a nephron deficit of 21 and 19% in male and female offspring, respectively. Mean arterial pressures were significantly elevated in offspring of both sexes from the CORT group. Real-time PCR revealed that CORT treatment increased expression of AT(1)Ra and AT(2)R at E16, and at PN30. Expression of AT(1)Rb was downregulated in embryonic life but upregulated at PN30. We believe that these results are the first to demonstrate that maternal CORT treatment results in a nephron deficit and development of hypertension in the rat offspring. Changes in the RRAS may be contributing to these phenotypes. Critically, this study suggests that increased but physiological levels of the natural glucocorticoid can programme similar changes to those seen with pharmacological doses of the synthetic glucocorticoid. This may have important implications for women experiencing significant stress during pregnancy.
- Subjects :
- Animals
Blood Pressure drug effects
Blood Pressure physiology
Corticosterone blood
Corticosterone pharmacology
Female
Fetal Development physiology
Gene Expression Regulation drug effects
Heart Rate drug effects
Heart Rate physiology
Humans
Hypertension physiopathology
Male
Nephrons drug effects
Nephrons embryology
Pregnancy
Prenatal Exposure Delayed Effects physiopathology
RNA, Messenger genetics
RNA, Messenger metabolism
Rats
Receptor, Angiotensin, Type 1 genetics
Receptor, Angiotensin, Type 2 genetics
Renin blood
Renin-Angiotensin System physiology
Corticosterone adverse effects
Hypertension etiology
Nephrons cytology
Prenatal Exposure Delayed Effects etiology
Receptor, Angiotensin, Type 1 physiology
Receptor, Angiotensin, Type 2 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3751
- Volume :
- 579
- Issue :
- Pt 2
- Database :
- MEDLINE
- Journal :
- The Journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 17204493
- Full Text :
- https://doi.org/10.1113/jphysiol.2006.125773