LAUSR

Objectives: Chromosome 2 (Chr2) introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt sensitive (SS) background (consomic SB2) reduced blood pressure (BP) and vascular inflammation under a normal-salt diet (NSD). BN Chr2 may contain genes that reduce vascular inflammation. The aim was to identify BN Chr2 genes that are anti-inflammatory under NSD and high-salt diet (HSD). Methods: Four-to-6 week-old male SS rats and congenic SB2a and SB2b rats containing different portions of BN Chr2 were fed a NSD or HSD (4% NaCl) for 8 weeks or until they developed a stroke as manifested by seizures. Systolic BP (SBP) was measured by telemetry. RNA was extracted from aorta and used for small and total RNA sequencing using Illumina HiSeq-2500. Sequences were mapped by STAR to Rattus norvegicus release-86 genome, annotated and counted by miRDeep2 for miRNA and HTSeq-count for mRNA and long non-coding RNA, and differential expression analysis done in R. Results: SBP was lower in SB2a and SB2b compared to SS (125 ± 3, 127 ± 6 vs 146 ± 2 mm Hg, P < 0.05) under NSD. SBP tended to be higher in SB2b but not in SB2a when compared to SS (185 ± 8, 167 ± 7 vs 168 ± 5 mm Hg) under HSD. Differentially expressed genes (DEGs) encoded in BN Chr2 introgressed portions were identified with fold change ≥1.5 and False discovery rate < 0.05. Ddah1 was commonly down-regulated in SB2a vs SS rats fed NSD and HSD while Acad9, Agtr1b, AABR07012047.1, Fbxw7, Ptgfrn were commonly down-regulated and AABR07012585.3, Bbs12, Kcnab1 up-regulated in SB2b vs SS rats fed NSD and HSD. Conclusion: BN Chr2 encoded DEGs were identified in aorta of congenic SB2a and SB2b rats fed NSD and HSD. Whether these genes play a role in vascular inflammation remains to be determined.