Role of Angiotensin II in Reactive Oxygen Species Production and Modulatory Role of Nitric Oxide (NO) in Vessel Responses to AngII in Acute Joint Inflammation in the Rabbit

Introduction: It has been approved that in most tissues NO production increases during acute inflammation and Angiotensin II has a role in production of reactive oxygen species (ROS). As regulation of joint blood flow (JBF) is important in this situation, this study was performed to investigate the interaction of local Ang II and ROS production and the modulatory role of NO on regulation of JBF during acute inflammation. Methods: The study was performed on ۲۴ Newzealand white rabbits divided into three experimental and one control groups. Acute knee joint inflammation was produced by intraarticular injection of ۰.۵ ml of a ۲% solution of carrageenan in knee joint. In the first group after ۲۴ hours animals were anesthetized by thiopental sodium and carotid artery, jugular vein and saphenous artery were cannulated for recording blood pressure, injection of L-NAME and local injection of AngII and losartan respectively. Blood flow was recorded by laser Doppler flow meter. Joint vascular resistance (JVR) was calculated by dividing arterial blood pressure (ABP) by JBF. In the second group, knee joint tissue was used for homogenization and ROS measurement .In the third group, Losartan (۱۰mg/kg) was administrated orally ۲ hours before induction of inflammation. Results: L-NAME increased JVR significantly. JVR in response to AngII was significantly increased. This response was significantly potentiated by L-NAME (P<۰.۰۱). Losartan completely blocked the effect of AngII on JVR. Data showed that total amount of antioxidant and catalase activity nonsignificantly increased in inflamed group. Losartan significantly returned the catalase activity of the inflamed joint to the control level(P<۰.۰۱). Conclusion: NO plays a role in the regulation of joint vascular tone and modulates the AT۱ receptor response to AngII in acutely inflamed joints. Ang II increased the production of ROS and as a result the amount of antioxidants in acutely inflamed joints and this is via angiotensin II and through AT۱ receptors.

Keywords:

Angiotensin II , nitric oxide , reactive oxygen species , acute inflammation , Carragenan , Knee joint , Rabbit