Angiotensin-(1-7) improves tail skin heat loss and increases the survival of rats with polymicrobial sepsis.

Sepsis is a serious syndrome, characterized by the excessive release of inflammatory mediators and thermoregulatory changes, being fever the most common sign. However, despite the importance of Angiotensin (Ang)-(1-7) in controlling the inflammation, the role of the peptide in the febrile response and mortality in animals submitted to experimental model of sepsis is still not clear. In this way, we evaluate the effect of continuous infusion of Ang-(1-7) in inflammatory response, thermoregulation and in mortality of Wistar male rats submitted to colonic ligation puncture (CLP). Before CLP surgery, the infusion pumps (Ang-(1-7), 1.5 mg/mL or saline) were inserted into the abdominal cavity and maintained for 24 h. CLP rats showed a febrile response starting from 3 h after and persisted until the 24th hour of experiment. Continuous treatment with Ang-(1-7) attenuated the febrile response and reestablished the euthermia 11 h after CLP, until the end of experiment, which coincided with an increased heat loss index (HLI). This effect was associated with a decrease in production of pro-inflammatory mediators in liver, white adipose tissue (WAT) and hypothalamus. Moreover, an increase in norepinephrine (NE) content in interscapular brown adipose tissue (iBAT) was observed in CLP animals, which was attenuated with treatment with Ang-(1-7), and decreased mortality in CLP animals treated with Ang-(1-7). Taken together, the present study demonstrates that continuous infusion treatment with Ang-(1-7) can promote a global anti-inflammatory effect, reestablishing the tail skin heat loss as a key thermo-effector function, resulting in an increased survival of animals submitted to experimental sepsis.

Lack of scarring is not always a sign of cardiac health: Functional and molecular characterization of the rat heart's following chronic reperfusion.

Even though the coronary reperfusion process is the most important tool to preserve cardiac function, after myocardial infarction, reperfusion of acutely ischemic myocardium can induce injury. We aimed to evaluate the functional and molecular aspects 4 weeks after myocardial ischemia-reperfusion (IR) in rats. Male Wistar rats (N = 47) were subjected to myocardial IR by short-term (30 min) ligation and subsequent reperfusion of the left descending coronary artery. Control rats (N = 7) underwent the same surgical maneuver without coronary ligation. After 4 weeks, rats had their cardiac function examined by ventricular pressure recording under basal condition or pharmacological stress. Myocardial fibrosis and molecular mediators of IR injury (reactive oxygen species, tumor necrosis factor-alpha and matrix-metalloproteinase-2) were assessed as well. Most of the rats subjected to IR did not show macroscopic signs of infarct, while only 17% of these animals showed large myocardial infarction scars. Of note, all animals submitted to IR presented the functional and molecular parameters altered when compared with the control subjects. Cardiac function was attenuated in all animals submitted to IR, regardless the presence or size of macroscopic cardiac scars. Interstitial fibrosis, matrix-metalloproteinase-2 activity and the expression of tumor necrosis factor-alpha were higher in the myocardium of all IR rats as compared to the control subjects (p<0.05). Myocardium superoxide anion and hydrogen peroxide were increased in rats without or with mild cardiac scars. These results show that IR leads to myocardial injury in rats. Besides, even the animals with an apparent healthy myocardium (without infarct scar) presented cardiac dysfunction and molecular changes that may contribute to the development of heart failure over time.