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The Importance of Angiotensin II Subtype Receptors for Blood Pressure Control During Mouse Pregnancy

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Abstract

Pregnancy is characterized by a progressive increase in the different components of the renin angiotensin system (RAS) including angiotensin II, a potent vasoconstrictor. Pregnant women and experimental animals are resistant to the pressor e fect of increased angiotensin II concentrations during pregnancy. In normal pregnancy, maternal blood pressure (BP) begins to fall in early gestation, reaches a nadir in midgestation, and then gradually increases to nonpregnant levels before term in both humans and C57BL/6J mice. The mechanism producing these changes is unknown. The present study investigates the roles of angiotensin II subtype receptors (AT1a and AT2) in hemodynamic regulation during pregnancy in mice. Female mice genetically or pharmacologically manipulated to alter angiotensin receptor stimulation were bred to 2 strains of males. Maternal BP was measured daily throughout pregnancy. Pup weight and number were determined. Pregnancy-induced hypertension was apparent in transgenic female mice expressing the human angiotensin gene bred with males expressing human renin. This e fect was not apparent in the absence of the AT1a receptor (ie, in AT1a knockout mice). The midgestation BP decline in both C56BL/6J and AT1a(—/—) females was abolished by AT2 receptor antagonism. There was a linear, inverse relationship between average BP throughout pregnancy and the average pup weight and number per litter. In summary, these findings suggest that activation of the AT2 receptor may be an important factor in promoting the midgestation BP decline that occurs in several mammalian species and, furthermore, that angiotensin is an important modulator of BP during pregnancy.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, 27157-1066, USA

    Kai Chen MD, David C. Merrill MD, PhD & James C. Rose PhD

  2. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

    James C. Rose PhD

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  1. Kai Chen MD
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  2. David C. Merrill MD, PhD
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  3. James C. Rose PhD
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Correspondence to James C. Rose PhD.

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Chen, K., Merrill, D.C. & Rose, J.C. The Importance of Angiotensin II Subtype Receptors for Blood Pressure Control During Mouse Pregnancy. Reprod. Sci. 14, 694–704 (2007). https://doi.org/10.1177/1933719107309060

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