4.6 Article Proceedings Paper

Temporal alterations in vascular angiotensin receptors and vasomotor responses in offspring of protein-restricted rat dams

Journal

Publisher

MOSBY-ELSEVIER
DOI: 10.1016/j.ajog.2012.04.010

Keywords

angiotensin; fetal programming; hypertension; intrauterine growth restriction; rats; vascular

Funding

  1. NHLBI NIH HHS [HL102866, R01 HL102866-01A1, R01 HL058144, R01 HL058144-13, HL 58144, R01 HL102866] Funding Source: Medline
  2. NICHD NIH HHS [R01 HD057013, R01 HD057013-01A2] Funding Source: Medline

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OBJECTIVE: Examine temporal alterations in vascular angiotensin II receptors (AT(1)R and AT(2)R) and determine vascular response to angiotensin II in growth-restricted offspring. STUDY DESIGN: Offspring of pregnant rats fed low-protein (6%) and control (20%) diet were compared. RESULTS: Prenatal protein restriction reprogrammed AT(1a)R messenger RNA expression in male rats' mesenteric arteries to cause 1.7- and 2.3-fold increases at 3 and 6 months of age associated with arterial pressure increases of 10 and 33 mm Hg, respectively; however, in female rats, increased AT1aR expression (2-fold) and arterial pressure (15 mm Hg) occurred only at 6 months. Prenatal protein restriction did not affect AT(2)R expression. Losartan abolished hypertension, suggesting that AT(1a)R plays a primary role in arterial pressure elevation. Vasoconstriction to angiotensin II was exaggerated in all protein-restricted offspring, with greater potency and efficacy in male rats. CONCLUSION: Prenatal protein restriction increased vascular AT(1)R expression and vasoconstriction to angiotensin II, possibly contributing to programmed hypertension.

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