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Int. J. Mol. Sci. 2014, 15(12), 23255-23268; doi:10.3390/ijms151223255

Long-Term Effects of Maternal Citrulline Supplementation on Renal Transcriptome Prevention of Nitric Oxide Depletion-Related Programmed Hypertension: The Impact of Gene-Nutrient Interactions

1
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
2
Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
3
Division of Nephrology, Departments of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
4
Department of Traditional Chinese Medicine, Chang Gung University, Linkow 244, Taiwan
*
Author to whom correspondence should be addressed.
Received: 4 November 2014 / Revised: 5 December 2014 / Accepted: 8 December 2014 / Published: 15 December 2014
(This article belongs to the Special Issue Gene-Nutrient Interactions)
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Abstract

Maternal malnutrition can elicit gene expression leading to fetal programming. l-citrulline (CIT) can be converted to l-arginine to generate nitric oxide (NO). We examined whether maternal CIT supplementation can prevent NG-nitro-l-arginine-methyl ester (l-NAME, NO synthase inhibitor)-induced programmed hypertension and examined their effects on the renal transcriptome in male offspring using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received l-NAME administration at 60mg/kg/day subcutaneously via osmotic minipump during pregnancy alone or with additional 0.25% l-citrulline solution in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to three groups: control, l-NAME, and l-NAME + CIT. l-NAME exposure induced hypertension in the 12-week-old offspring, which CIT therapy prevented. Identified differentially expressed genes in l-NAME and CIT-treated offspring kidneys, including Guca2b, Hmox1, Hba2, Hba-a2, Dusp1, and Serpine1 are related to regulation of blood pressure (BP) and oxidative stress. In conclusion, our data suggests that the beneficial effects of CIT supplementation are attributed to alterations in expression levels of genes related to BP control and oxidative stress. Our results suggest that early nutritional intervention by CIT has long-term impact on the renal transcriptome to prevent NO depletion-related programmed hypertension. However, our RNA-Seq results might be a secondary phenomenon. The implications of epigenetic regulation at an early stage of programming deserve further clarification. View Full-Text
Keywords: citrulline; developmental programming; epigenetic regulation; hypertension; next generation sequencing; nitric oxide citrulline; developmental programming; epigenetic regulation; hypertension; next generation sequencing; nitric oxide
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Tain, Y.-L.; Lee, C.-T.; Huang, L.-T. Long-Term Effects of Maternal Citrulline Supplementation on Renal Transcriptome Prevention of Nitric Oxide Depletion-Related Programmed Hypertension: The Impact of Gene-Nutrient Interactions. Int. J. Mol. Sci. 2014, 15, 23255-23268.

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