Role of immune factors in angiotensin II-induced hypertension and renal damage in Dahl salt-sensitive rats

Abstract

The present study assessed the importance of immunity in angiotensin (ANG) II (5 ng·kg−1·min−1 iv)-mediated hypertension in Dahl salt-sensitive (SS) rats and SS rats deficient in T and B lymphocytes (SSRag1−/−) fed a 0.4% NaCl diet. Baseline mean arterial blood pressure (MAP) was not different between groups. ANG II infusion significantly increased MAP in both groups, although MAP increased more rapidly in SS rats, and the maximal MAP achieved was significantly greater in SS than SSRag1−/− rats (190 ± 3 vs. 177 ± 3 mmHg) after 12 days. Renal damage, as assessed by albumin excretion rate, was significantly increased after 12 days of ANG lI infusion in SS (from 32 ± 4 to 81 ± 9 mg/day) and SSRag1−/− (from 12 ± 2 to 51 ± 8 mg/day) rats; albumin excretion rate was significantly different between SS and SSRag1−/− rats at all points measured. After 9 days of recovery from ANG II, MAP was decreased to a greater extent in SSRag1−/− than SS rats (143 ± 5 vs. 157 ± 8 mmHg) compared with the peak MAP during ANG II infusion. At this same time point, albumin excretion rate was significantly lower in SSRag1−/− than SS rats (42 ± 8 vs. 66 ± 7 mg/day). Further studies demonstrated an increase in CD45+ total leukocytes, CD11b/c+ macrophages/monocytes, and CD3+ T cells in kidneys of ANG II- compared with vehicle-treated SS rats. The present data suggest that infiltrating T cells in the kidney exacerbate renal damage in ANG II-induced hypertension in SS rats maintained on a 0.4% NaCl diet, similar to results observed with a salt stimulus in SS rats.