Role of ascorbic acid in distribution of connexins in renin angiotensin system of lipopolysaccharide-treated rats

Endotoxemia is a process, which is caused by a bacterial infection existing in blood and spreading one tissue to another, which causes excessive damage. This is characterized with hypotension, decreasing response to vasoconstrictor agets, myocardial disorder, organs' blood feeding disorder and intravascular coagulopathy. Endotoxemia causes acute renal failure, hemodynamic disturbance, hypo perfusion, kidney perfusion, and decrease on glomerular filtration and increase on kidneys' vascular resistance. In Endotoxemia, both the incidents that take place depending on the infection and the changes in the circulatory causes several systems including Renin Angiotensin System (RAS) to be stimulated. RAS has an important role in regulating blood pressure and homeostasis, the volume physiologically and in pathogenesis of cardiovascular diseases. Connexin (Cx) proteins that form gap junctions (GJ) are found in endothelium cells, straight vein muscle cells and juxtaglomerular apparatus in the kidney and it is known that it has a role in regulating RAS. GJs are connections between cells, which is formed by Cx proteins that are connecting each other tight. GJ has a great importance on many tissues and organs, especially on connection between cells and providing homeostasis in epithelium muscle cells and nerve tissue. In Endotoxemia, there is not enough data about the effects of ascorbic acid (AA), which is an antioxidant whose protective effects in the events of oxidative damage and inflammation on distribution of connexions in the RAS. In this study, in the Endotoxemia model, which is formed by applying LPS, it is aimed to make a research about the effects of RAS and connexins. In the study, 30 three months old adult male albino rats were used. The animals have bewere divided into four groups as control, LPS (2 mg/kg, intravenous (iv)), LPS+AA (2 mg/kg LPS, iv and 100 mg/kg AA, iv) and AA (100 mg/kg, iv). Cannulas have been installed to the animals in order to measure their hemodynamic data (Main Arterial Pressure (MAP) and heartbeat, one to femoral artery to take blood samples, one to jugular vein for infusion of anesthesia and to right femoral vein to apply injections. The blood parameters, which have been taken before applying LPS (T0 at the beginning of the experiment) at the end LPS infusion (T1), after an hour LPS infusion (T2) and at the end of the experiment (T3), pH, cHCO3- ( P, st) (standard bicarbonate), cBase (Ecf) (standard base excess), pCO2 (partial carbon dioxide pressure), cNa+ (sodium), cCl- (chlorine), cGlu (D-glucose concentration in plasma) and cLac (L- Lactate concentration in plasma) levels have been measured. In blood and kidney samples that have been taken at the end of the experiment. Biochemically renin, angiotensin II (Ang II), Cx40 and Cx43 have been measured. Moreover, distribution of cx40 in the kidney have been examined immunohistochemically. The data obtained have been evaluated statistically. In LPS group, which was formed, Endotoxemia by LPS application decrease in mean arterial pressure but it has been observed that AA application has not caused any changes. It has been detected that there is no meaningful change of heartrate among the groups. In LPS groups, decrease in values of pH, cHCO3- , base excess and glucose values and increase in cNa+ and Lactate value. In LPS+AA group compared to the control group, increase in lactate and cCl- , decrease in pH, cHCO3, base excess and glucose values have been detected. In LPS groups, increase in renin and Ang II values in plasma and tissue and similarity in Cx40 and Cx43 values with the control group. In LPS+AA group, decrease has been detected in renin and Ang II levels compared to the LPS group and no change in Cx40 and Cx43 value an similarity with control group. When we look at the distribution of Cx40 reaction immunohistochemically, it has been detected that the reaction has never shown any meaningful change in LPS applied groups, only increase in AA group has been detected. In conclusion, it has been seen that RAS has been stimulated depending on the decrease in the blood pressure in the Endotoxemia model, which has been formed by LPS application. It has been detected that AA has no effect on blood pressure but has an effect on RAS. In the Endotoxemia model, it has not been detected any meaningful change when Cx proteins observed. To sum up, in order to reveal the connection between RAS and connexins in Endotoxemia, to make more research on different experimental models is going make a huge contribution to be understood the role of RAS on pathophysiological incidents.