Abstract P227: Mapping of Chromosome 2 Regions Linked to Vascular Inflammation Using Congenic Rats

Abstract

Objective: Chromosome 2 (chr2) introgression from normotensive Brown Norway rats (BN) into hypertensive Dahl salt sensitive (SS) background (consomic SS2 BN ) reduced blood pressure (BP) and vascular inflammation under a normal-salt diet. Mapping of chr2 using congenic rats revealed that the distal portion of BN chr2 (SS2 BN a) but not the middle segment (SS2 BN b) on the SS background under a normal-salt diet contains anti-inflammatory genes. However, the role of chr2 in the regulation of vascular inflammation under a high-salt diet (HSD) remains unknown. We hypothesized that SS2 BN a but not SS2 BN b rats would have reduced vascular inflammation under HSD. Design and method: Four-to-6 week old male SS, SS2 BN a and SS2 BN b rats were fed a HSD (4% NaCl) for 8 weeks or until they developed a stroke as manifested by seizures. Vascular remodeling was assessed in mesenteric arteries (MA) using pressurized myography. Reactive oxygen species (ROS) production by dihydroethidium staining, vascular cell adhesion molecule (VCAM)-1 expression and CD3 + T cell infiltration by immunofluorescence were determined in aorta or perivascular adipose tissue (PVAT). BP was measured by telemetry after 6 weeks of HSD. Results: Systolic BP tended to be higher in SS2 BN b compared to SS (185±8 vs 168±5 mmHg). The incidence of seizures was 3.9-fold higher in SS2 BN b compared to SS (12/36 vs 3/35 rats ( P <0.05). MA media/lumen was 1.3-fold higher in SS2 BN a compared to SS (10.6±0.9 vs 7.9±0.4%, P <0.01). PVAT ROS production was 1.8-fold higher in SS2 BN a compared to SS (5.6±0.8 vs 3.2±0.1 relative fluorescence units [RFU]/μm 2 , P <0.01) and tended to be lower in SS2 BN b (2.1±0.4 vs 3.2±0.1 RFU/μm 2 ). Aortic VCAM-1 was increased 2.1-fold in SS2 BN a compared to SS (2.6±0.5 vs 1.2±0.3 RFU/μm 2 , P <0.05). Aortic PVAT CD3 + T cell infiltration was 55% lower in SS2 BN b compared to SS (17±4 vs 38±4 cells/mm 2 , P <0.05). Conclusions: Unexpectedly, SS2 BN a rats present increased vascular injury under HSD. The absence of vascular inflammation and remodeling in SS2 BN b rats despite slightly higher BP seems maladaptive and may explain the increased incidence of stroke.