Angiotensin II receptor antagonist reduces subsequent uterine arterial dysfunction in pregnant offspring of protein-restricted rat dams

Saito, Tomomi, Musha, Yuka, Miyakawa, Miho, Itoh, Shigeru, Ohtsuji, Mareki, Hanson, Mark A. and Takeda, Satoru (2012) Angiotensin II receptor antagonist reduces subsequent uterine arterial dysfunction in pregnant offspring of protein-restricted rat dams. Journal of Obstetrics and Gynaecology Research, 38 (3), 483-489. (doi:10.1111/j.1447-0756.2011.01737.x). (PMID:22381101)

Abstract

Aim: a low-protein diet (LPD) during pregnancy induces vascular dysfunction and hypertension in the offspring, prevented by administration of an angiotensin II type 1 (AT1) receptor antagonist in early life to the offspring. Whether such protection extends to subsequent pregnancy is unknown; we therefore hypothesized that administration of a specific AT1 receptor antagonist (losartan) in early life to offspring of LPD dams would improve vascular dysfunction in their uterine arteries when they, in turn, were pregnant.

Methods: pregnant rats were randomly divided into two dietary groups fed a control (C) or protein-restricted
(R) diet throughout pregnancy. Between two and 10 weeks postnatally, female offspring (F1) were randomly assigned to drink either pure tap water (CO, RO) or water with losartan (CL, RL). Offspring were mated and killed on gestational day 19 or 20 in order to investigate uterine artery function.

Results: in pregnant offspring, vasoconstriction of the uterine arteries to phenylephrine (PE) and the thromboxane A2 mimetic U46619 was greater in RO than CO (F1). Responses to both antagonists were suppressed in RL (F1). Relaxation to sodium nitroprusside was increased in RO versus CO and suppressed in RL versus RO (F1).

Conclusion: administration of an AT1 receptor antagonist to offspring during the suckling and juvenile period improves the uterine vascular dysfunction in pregnancy induced by prior maternal LPD during their development. Such treatment may contribute to decreasing the transmitted risks of maternal malnutrition from offspring to the subsequent generation.

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Contributors

Author: Mark A. Hanson

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