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·min iv)-mediated hypertension in Dahl salt-sensitive (SS) rats and SS rats deficient in T and B lymphocytes (SS) 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 SS 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 SS (from 12 ± 2 to 51 ± 8 mg/day) rats; albumin excretion rate was significantly different between SS and SS rats at all points measured. After 9 days of recovery from ANG II, MAP was decreased to a greater extent in SS 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 SS 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.

Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury

“…For example, in the current study, IL-17 expression was elevated in response to Ang II and elevated Na + in vitro and was dependent on SOCE activity. Recent studies have shown that Ang II-dependent hypertension is, in part, dependent on IL-17 activity (36,37); whether Orai1 modulates Ang II-dependent Th17 responses in these models remains to be determined.…”

Dietary influences on the Dahl SS rat gut microbiota and its effects on salt‐sensitive hypertension and renal damage

“…Wilck et al have attributed the salt-sensitive hypertensive effects in a model of autoimmune encephalomyelitis to a depletion in Lactobacillus murinus, which occurs in a T helper 17 (T H 17) cell-dependent manner. 32 Interestingly, we have only observed IL-17 effects in an angiotensin II-induced model in the Dahl SS rat, 36 and instead have determined that mechanisms related to IL-6 signaling 37 and NOX2-derived free radical production in immune cells 38 appears to drive salt-sensitivity. The gut dysbiosis observed in both hypertensive human subjects and experimental mice has more recently been associated with increased intestinal inflammation and activation of antigen presenting cells.…”

Effects of Caloric Restriction Diet on Arterial Hypertension and Endothelial Dysfunction

“…The classic definition has been revised as the immune cells contribute to determining kidney organ damage. In fact, it has been highlighted how different stimuli, including an increase in angiotensin II production or a diet with a high salt content, can induce a response by the immune system that causes an inflammatory reaction mainly at the level of the organs involved in the control of BP values (such as kidneys, heart and nervous system) [ 103 , 104 , 105 ]. This observation is confirmed by the fact that hypertensive patients usually present a low-grade chronic inflammatory state.…”