Abstract P337: Sodium-independent Elevations of Blood Pressure are Accompanied by Immune Cell Infiltration in the Kidney and Renal Damage in Dahl SS Rats

Abstract

Infiltration of immune cells in the kidney is driven by elevated renal perfusion pressure and amplifies sodium-sensitive hypertension and renal injury in Dahl Salt Sensitive (SS) rats fed a high salt diet. The present studies were performed to determine the importance of immunity in the development of sodium-independent hypertension and renal damage in SS rats and SS lacking T- and B-lymphocytes due to a null mutation in the Rag1 gene (SS-Rag1 em1Mcwi ). The baseline level of mean arterial pressure (MAP) was not different between groups, and the continuous infusion of AngII (5 ng/kg/min, iv) to SS and SS-Rag1 em1Mcwi fed low salt (0.4% NaCl) led to a significantly greater increase in MAP in SS (190±3 mmHg) than in SS-Rag1 em1Mcwi (177±3 mmHg) after 12 days of infusion (n=9 rats/group). Renal damage, as assessed by albumin excretion rate, was significantly increased after 12 days of AnglI infusion in the SS (from 32±4 to 81±9 mg/day) and in the Rag1 mutants (from 12±2 to 51±8 mg/day). Compared to vehicle-infused rats, kidneys of AngII-treated SS (n=4-5/group) had increased CD45+ total leukocytes (1.8±0.2 vs 4.4±1.2 x 10 6 cells/kidney), including CD11b/c+ macrophages/monocytes and CD3+ T Cells. Upon cessation of the AngII infusion, MAP in the SS-Rag1 em1Mcwi significantly decreased to a level not different from control values (135±5 vs 128±3 mmHg). In contrast, though MAP decreased in the SS when AngII infusion was stopped, blood pressure remained at a level greater than control values throughout the 9-day recovery period (157±8 vs 129±2 mmHg). Albumin excretion rate also tended to decrease in both SS and SS-Rag1 em1Mcwi rats following the return to saline infusion, but the reversibility was not complete. Despite the maintenance of elevated pressure in the SS following AngII withdrawal, there was a significant and complete reversal in the number of CD45+, CD11b/c+, and CD3+ cells in the SS kidneys. The present data indicate that immune cells amplify sodium-independent hypertension and the development of renal damage in the SS rat, but also indicate that factors in addition to renal perfusion pressure may mediate immune cell infiltration into the kidney in hypertension.