Abstract
Hypertensive rats subjected to chronic intracerebroventricular (ICV) infusion of angiotensin-(1-7) [Ang-(1-7)] presented attenuation of arterial hypertension, improvement the baroreflex sensitivity and restoration of cardiac autonomic tonus. In the present study we evaluated whether chronic increase in Ang-(1-7) in the brain modulates inflammatory mediators in the hypothalamus of the transgenic hypertensive rats that present overexpression of renin [(mRen2)27; TGR]. Sprague Dawley (SD) and TGR were subjected to 14 days of ICV infusion of Ang-(1-7) (200 ng/h) or 0.9% sterile saline (0.5 μl/h) through osmotic mini-pumps. The animals were euthanized by decapitation and the hypothalamus was quickly removed and frozen on dry ice. Cytokine levels were evaluated through Elisa assay and enzymes of RAS were measured by fluorimetric assays. As expected, levels of pro-inflammatory cytokines (IL-1α, IL-6 and TNF-α) were increased in TGR (48 ± 3.5 pg/mg, 61 ± 2.7 pg/mg, 76 ± 4.3 pg/mg, respectively) as compared to SD rats (23 ± 1.8 pg/mg, 38 ± 3.4 pg/mg, 39 ± 3.5 pg/mg, respectively), while IL-10 was not altered. Interestingly, ICV infusion of Ang-(1-7) reduced levels of TNF-α (48 ± 3.4 pg/mg vs 76 ± 4.3 pg/mg in untreated TGR) and increased the levels of IL-10 (32 ± 2.6 pg/mg vs 19 ± 1.2 pg/mg in untreated TGR), without affecting IL-1α or IL-6 levels. No difference was found in ACE activity in plasma, on the other hand, the increased ACE activity in the hypothalamus of TGR (207 ± 25.5 nmoles His-Leu/ min/ mg of protein vs 173 ± 13.0 nmoles His-Leu/ min/ mg of protein, in SD rats) was significantly reduced (134 ± 7.9 nmoles His-Leu/ min/ mg of protein) by ICV infusion of Ang-(1-7). These data show that long term increase in Ang-(1-7) levels in the brain modulates inflammatory mediators in the hypothalamus, suggesting a possible additional mechanism for Ang-(1-7) antihypertensive action in the central nervous system.
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