Alamandine Counteracts Inflammation in the Central Nervous System of Hypertensive Animals.

Abstract

Alamandine, a new peptide of the renin‐angiotensin system (RAS), has shown similar biological actions of angiotensin‐(1‐7). In SD rats, alamandine produced stimulatory effects when microinjected into medullary areas involved in sympathetic control. On the other hand, lateral ventricle (ICV) infusion of alamandine improved the baroreflex sensitivity of normotensive rats. We investigated the effect of long‐term central increase of alamandine on the arterial pressure (AP) of transgenic TGR(mREN2)27 (TG) hypertensive rats. Twelve weeks old SD and TG rats (Protocol 239/2016, CEUA/UFMG) instrumented with telemetry probes for AP measurement, underwent 28 days of ICV infusion of alamandine (TG+Ala, 200 ng/h) or saline (TG+Sal and SD+Sal; Control; 0.25 μL/h) through osmotic mini‐pumps. The levels of inflammatory cytokines (TNF‐α, IL‐6, IL‐1β, and IL‐10) in hypothalamus and medulla oblongata was determined by ELISA. Long‐term ICV infusion of alamandine produced a small decrease in Mean AP (ΔMAP: −16±8 mmHg, n=5, p<0.05) of TG rats from the first week of treatment, while control rats (TG+Sal) presented an increase in the AP during the same period of time (ΔMAP: +17±7 mmHg, n=5, p<0.05). Alamandine infusion did not alter baseline heart rate or the circadian rhythm of AP or heart rate in TG rats. Further, TG+Sal presented increased levels of TNF‐α, IL‐6, and IL‐1β in the hypothalamus and medulla oblongata. Interestingly, long‐term ICV infusion of alamandine attenuated levels of TNF‐α (SD+Sal: 29.2±3.1 pg/100 mg of protein; TG+Sal: 73.1±2.9 pg/100 mg of protein; and TG+Ala: 49.3±0.4 pg/100 mg of protein; n=4–7, p<0.001) and IL‐6 (SD: 26.8±1.2 pg/100 mg of protein; TG+Sal: 65.5±4.3 pg/100 mg of protein; and TG+Ala: 42.3±1.8 pg/100 mg of protein; n=4–7, p<0.001) in the hypothalamus and the levels of TNF‐α (SD: 23.5±2.0 pg/100 mg of protein; TG+Sal: 56.9±4.5 pg/100 mg of protein; and TG+Ala: 40.2±1.2 pg/100 mg of protein; n=4–7, p<0.01) in the medulla oblongata of TG hypertensive rats. Treatment with alamandine also increased the levels of IL‐10 (SD: 20.0±0.7 pg/100 mg of protein; TG+Sal: 19.2±0.52 pg/100 mg of protein; and TG+Ala: 24.2±1.4 pg/100 mg of protein; n=4–7, p<0.05) in the hypothalamus of TG rats. Our data show that long‐term ICV infusion of alamandine has anti‐inflammatory effect in areas related to cardiovascular control in transgenic hypertensive rats. This effect was associated with a decrease in AP of these animals. Our data suggest alamandine as an alternative route for the RAS in the central control of AP.Support or Funding InformationFAPEMIG, CNPq, INCT‐Nanobiofar, CAPES/DAAD (PROBRAL), and FAPEMIG/CNPq (Universal Projects to MJC‐S)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.