2009 Southern Regional Meeting Abstracts

Purpose of Study: Aldosterone/salt treatment (ALDOST) leads to a proinflammatory vasculopathy involving lymphocytes that contributes to hypertension and cardiac pathology. The thymus, integral to lymphocyte processing, undergoes accelerated involution during ALDOST. Hypozincemia and/or the release of corticosterone by an activated hypothalamic-pituitary-adrenal axis may each be contributory. Thymulin (Thy) production, a Zn²⁺-dependent anti-inflammatory cytokine released by the thymus, may decline to favor a proinflammatory phenotype. Herein, we addressed the potential role of thymic involution and loss of thymulin on the hypertension and cardiac fibrosis associated with ALDOST.
Methods Used: Eight-wk-old male Sprague-Dawley rats receive ALDOST (0.75 μg/h by implanted minipump), together with 1% NaCl/0.4% KCl in drinking water for 4 wks. In addition, 4 cotreatments were studied: RU486, a glucocorticoid receptor antagonist (8 mg/day by gavage); a Zn²⁺ supplement alone (dietary, 40 mg/day); an infusion of Thy alone (0.7 μg/day) or in combination with ZnSO₄. Age-/gender-matched rats served as controls. We monitored: systolic blood pressure(SBP); thymus weight; plasma Thy; and collagen volume fraction (CVF; %), a marker of fibrosis.
Summary of Results: Compared to controls, SBP was elevated (p<0.05) by ALDOST (107±7 vs. 195±8 mm Hg) and was not reduced by cotreatment with RU486, ZnSO₄, thymulin, or Thy+ZnSO₄. Thymic weight was reduced (p<0.05) compared to controls (0.18±0.02 vs. 0.58±0.05 mg) and this involution was not prevented by any of the cotreatments. Plasma Thy was reduced (p<0.05) compared to controls (0.43±0.01 vs. 0.55±0.06 ng/mL) and was restored by Thy infusion alone or Thy+ZnSO₄ (0.50±0.08 and 0.53±0.02 ng/mL), but not ZnSO₄. The rise in CVF seen at 4 wk ALDOST (8.6±1.7% vs. 2.4±0.6% controls; p<0.05) was not prevented by any cotreatment.
Conclusions: An accelerated involution of the thymus and reduced plasma Thy accompanied ALDOST and were not prevented by cotreatment with ZnSO₄, Thy, or RU486. The hypertension and fibrosis seen at wk 4 ALDOST was not prevented by cotreatment with ZnSO₄ or Thy alone or in combination. These findings suggest the thymus and Thy do not contribute to the proinflammatory phenotype.