Prenatal dexamethasone leads to both endothelial dysfunction and vasodilatory compensation in sheep

Judit Molnar, David C. Howe, Mark J.M. Nijland, Peter W. Nathanielz

Research output: Contribution to journalReview article

54 Scopus citations

Abstract

We investigated long-term cardiovascular effects in the offspring of sheep exposed to prenatal dexamethasone (DM). We assessed in vitro vascular responsiveness and evaluated endothelial nitric oxide synthase (eNOS) message and protein levels in femoral muscle removed from 5-month-old sheep. Dexamethasone was administered i.m. to pregnant ewes as 3 weekly courses (4 × 2 mg at 12 h intervals), starting on day 103 of gestation (term ∼149 days). Ewes were allowed to lamb. At 5 months of age a carotid catheter was placed for blood pressure measurement and hamstring muscle was removed from the lambs under general anaesthesia. We demonstrate that following prenatal DM exposure in the 5-month-old offspring: (1) blood pressure is unchanged; (2) as previously reported in the fetus, sensitivity to endothelin-1 (ET) is increased; (3) acetylcholine-induced relaxation is increased; (4) L-NAME suppressible vasodilatory response to ET is abolished; (5) there is no change in endothelium-independent vasodilatation; and (6) there is no change in eNOS RNA and protein levels, when compared to saline treated controls. We speculate that decreased agonist-induced NO release is not due to alteration in gene expression, but is more likely to be a post-transcriptional event. In summary, the lack of a difference in resting mean arterial pressure (MAP) between DM and control lambs indicates that the compensation we have previously demonstrated in the fetus following glucocorticoid exposure persists to 5 months postnatal age. Compensation is likely due to non-NO-dependent mechanisms, since no evidence was found of upregulated NOS.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalJournal of Physiology
Volume547
Issue number1
DOIs
StatePublished - Feb 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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