Consequences of perinatal treatment with L-arginine and antioxidants for the renal transcriptome in spontaneously hypertensive rats.
Treating spontaneously hypertensive rats (SHR) with L-arginine, taurine, and vitamins C and E (ATCE) during nephrogenesis (2 weeks before to 4 weeks after birth) persistently lowers blood pressure. Hypothetically, differential gene expression in kidney of SHR vs. normotensive Wistar-Kyoto rats (WKY) is partially corrected by maternal ATCE in SHR. Differential gene expression in 2-days, 2-weeks, and 48-week-old rats was studied using oligonucleotide chips. Transcription factor binding sites (TFBS) of differentially expressed genes were analyzed in silico. Differential gene expression varied between SHR+ATCE and SHR, suggesting both direct and indirect effects; but, few genes were modulated toward WKY level and there was little overlap between ages. TFBS analysis suggests less Elk-1-driven gene transcription in both WKY and SHR+ATCE vs. SHR at 2 days and 2 weeks. Concluding, in SHR, persistent antihypertensive effects of maternal ATCE are not primarily due to persistent corrective transcription. Less Elk-1-driven transcription at 2 days and 2 weeks may be involved.
Wesseling
Sebastiaan
S
Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Koeners
Maarten P
MP
Kantouh
Farid
F
Joles
Jaap A
JA
Braam
Branko
B
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001120:Arginine / Q000008:administration & dosage*; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014157:Transcription Factors / Q000378:metabolism*
D000975:Antioxidants; D020543:Proteome; D014157:Transcription Factors; D001120:Arginine