Alterations in hypothalamic synaptophysin and death markers may be associated with vasopressin impairment in sepsis survivor rats.

Abstract

The impairment in arginine vasopressin (AVP) secretion during sepsis is described in clinical and experimental studies and has been associated with oxidative stress, apoptosis, and diminished activation of hypothalamic neurons. Few studies have, however, assessed these abnormalities in sepsis survivors. Here we performed two sets of experiments on Wistar rats that had been subjected to sepsis by cecal ligation and puncture (CLP) or nonmanipulated (naive) as control. In the first set, tissues and blood were collected from survivor rats 10 days after CLP to quantify hypothalamic Bcl-2, cleaved caspase- 3 and synaptophysin content, and bacterial load. In the second set, survivor rats were submitted to an acute osmotic stimulus (hypertonic saline), and after 30 minutes the water intake and AVP secretion were analyzed. The sepsis-surviving rats did not show bacterial load in tissues, but their hypothalamic synaptophysin and Bcl-2 levels were decreased, and the cleaved caspase- 3 level was increased when compared with the control group. However, AVP secretion was significantly attenuated in the CLP survivor animals submitted to an acute osmotic stimulus. These results suggest that the persistent AVP impairment in sepsis survivor animals may be due to a hypothalamic dysfunction associated with a synaptic deficit and decreased anti-apoptotic protein expression. This article is protected by copyright. All rights reserved.