Dataset Information

Impact of AT2 receptor deficiency on postnatal cardiovascular development.

ABSTRACT:

Background

The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear.

Methodology/principal findings

Hearts from 1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were recorded and echocardiographic analysis of cardiac function as well as telemetric blood pressure measurements were performed. Moreover, gene expression, sarcomere shortening and calcium transients were examined in ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an accelerated body weight gain and a reduced heart to body weight ratio as compared to WT mice in the postnatal period. However, in adult KO mice the heart to body weight ratio was significantly increased most likely due to elevated systemic blood pressure. At postnatal day 7 ventricular capillarization index and the density of ?-smooth muscle cell actin-positive blood vessels were higher in KO mice as compared to WT mice but normalized during adolescence. Echocardiographic assessment of cardiac systolic function at postnatal day 7 revealed decreased contractility of KO hearts in response to beta-adrenergic stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere shortening and an increased peak Ca(2+) transient in response to isoprenaline when stimulated concomitantly with angiotensin II.

Conclusion

The AT2 receptor affects postnatal cardiac growth possibly via reducing body weight gain and systemic blood pressure. Moreover, it moderately attenuates postnatal vascularization of the heart and modulates the beta adrenergic response of the neonatal heart. These AT2 receptor-mediated effects may be implicated in the physiological maturation process of the heart.

SUBMITTER: Biermann D

PROVIDER: S-EPMC3483305 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Impact of AT2 receptor deficiency on postnatal cardiovascular development.

Biermann Daniel D Heilmann Andreas A Didié Michael M Schlossarek Saskia S Wahab Azadeh A Grimm Michael M Römer Maria M Reichenspurner Hermann H Sultan Karim R KR Steenpass Anna A Ergün Süleyman S Donzelli Sonia S Carrier Lucie L Ehmke Heimo H Zimmermann Wolfram H WH Hein Lutz L Böger Rainer H RH Benndorf Ralf A RA

PloS one 20121029 10

<h4>Background</h4>The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear.<h4>Methodology/principal findings</h4>Hearts from 1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were ...[more]

PMID: 23144713

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Project description:This review summarizes the latest findings, from animal models and clinical studies, regarding the cardiovascular and metabolic consequences in adult life of zinc deficiency (ZD) during prenatal and early postnatal life. The effect of zinc supplementation (ZS) and new insights about sex differences in the phenotype and severity of cardiovascular and metabolic alterations are also discussed. Zinc has antioxidant, anti-inflammatory, and antiapoptotic properties and regulates the activity of enzymes involved in regulation of the metabolic, cardiovascular, and renal systems. Maternal ZD is associated with intrauterine growth restriction and low birth weight (LBW). Breast-fed preterm infants are at risk of ZD due to lower zinc uptake during fetal life and reduced gut absorption capacity. ZS is most likely to increase growth in preterm infants and survival in LBW infants in countries where ZD is prevalent. Studies performed in rats revealed that moderate ZD during prenatal and/or early postnatal growth is a risk factor for the development of hypertension, cardiovascular and renal alterations, obesity, and diabetes in adult life. An adequate zinc diet during postweaning life does not always prevent the cardiovascular and metabolic alterations induced by zinc restriction during fetal and lactation periods. Male rats are more susceptible to this injury than females, and some of the mechanisms involved include: 1) alterations in organogenesis, 2) activation of oxidative, apoptotic, and inflammatory processes, 3) dysfunction of nitric oxide and renin-angiotensin-aldosterone systems, 4) changes in glucose and lipid metabolism, and 5) adipose tissue dysfunction. Safeguarding body zinc requirements during pregnancy, lactation, and growth periods could become a new target in the prevention and treatment of cardiovascular and metabolic disorders. Further research is needed to elucidate the efficacy of ZS during early stages of growth to prevent the development of these diseases later in life.

Dataset Information

Impact of AT2 receptor deficiency on postnatal cardiovascular development.

Background

Methodology/principal findings

Conclusion

Publications

Impact of AT2 receptor deficiency on postnatal cardiovascular development.

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