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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Physiology 1/2015

Antenatal maternal low protein diet: ACE-2 in the mouse lung and sexually dimorphic programming of hypertension

Zeitschrift:
BMC Physiology > Ausgabe 1/2015
Autoren:
Ravi Goyal, Jonathan Van-Wickle, Dipali Goyal, Lawrence D. Longo
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12899-015-0016-6) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

Conception and Design: RG and LDL. Acquisition of Data and Analysis/Interpretation of Data: RG, JVW, DG. Drafting of the manuscript and revising it critically: RG and LDL. Final Approval: RG and LDL. All authors read and approved the final manuscript.

Abstract

Elevated blood pressure is an important global health problem, and in-utero under-nutrition may be an important factor in the pathogenesis of hypertension. In the present study, we tested the hypothesis that antenatal maternal low protein diet (MLPD) leads to sexually dimorphic developmental programming of the components of the pulmonary renin-angiotensin system. This may be important in the antenatal MLPD-associated development of hypertension. In pregnant mice, we administered normal (control) and isocaloric 50 % protein restricted diet, commencing one week before mating and continuing until delivery of the pups. From the 18th to 24th week postnatal, we measured blood pressure in the offspring by use of a non-invasive tail-cuff method. In the same mice, we examined the mRNA and protein expression of the key components of the pulmonary renin-angiotensin system. Also, we examined microRNA complementary to angiotensin converting enzymes (ACE) 2 in the offspring lungs. Our results demonstrate that as a consequence of antenatal MLPD: 1) pup birthweight was significantly reduced in both sexes. 2) female offspring developed hypertension, but males did not. 3) In female offspring, ACE-2 protein expression was significantly reduced without any change in the mRNA levels. 4) miRNA 429, which has a binding site on ACE-2 - 3’ UTR was significantly upregulated in the female antenatal MLPD offspring. 5) In males, ACE-2 mRNA and protein expression were unaltered. We conclude that in the mouse, antenatal MLPD-induced reduction of ACE-2 in the female offspring lung may be an important mechanisms in sexually dimorphic programming of hypertension.
Zusatzmaterial
Additional file 1: Table S1. Composition of the diet administered to control group of mice dams. Table S2 Composition of the diet administered to the antenatal maternal low protein group of mice dams.
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