Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and hypertension in the rat offspring

Reetu Ragni Singh, Luise Anne Cullen-McEwen, Michelle Monica Kett, Wee Ming Boon, John P Dowling, John Frederick Bertram, Karen Margaret Moritz

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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/day) 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 on 3) receptors of renal renin-angiotensin system (RRAS); AT1Ra, AT1Rb and AT2Ra, during both, embryonic (E16, E20) and adolescent (PN30) life. Plasma CORT concentrations were approximately doubled 30 minutes 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 AT1Ra and AT2R at E16 and at PN30. Expression of AT1Rb was down-regulated in embryonic life but upregulated at PN30. These results for the first time 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 program similar changes to those seen with pharmacological doses of the synthetic one. This may have important implications for women experiencing significant stress during pregnancy.
Original languageEnglish
Pages (from-to)503 - 513
Number of pages11
JournalThe Journal of Physiology
Volume579
Issue number2
Publication statusPublished - 2007

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