Investigation of Response to Angiotensin II (Ang II) and its Receptor Subtypes in Acutely Inflamed Joint Blood Vessels in Rabbit

Abstract: Introduction: Inflammatory joint diseases are common in elderly, and regulation of joint blood flow (JBF) is important in these conditions. The aim of this study was to investigate the response of inflamed joint blood vessels to angiotensin II (Ang II), a vasoconstrictor factor which has been shown to be produced in inflamed joints locally. Identification of Ang II receptor subtypes in joint blood vessels was the second goal of this study. Methods: The present study was performed on 12 Newzland white rabbits. Acute knee joint inflammation was produced by intraarticular injection of 0.5 ml of a 2% of carrageenan solution 24 hours before the experiment. On experiment day, animals were anaesthetized by thiopental sodium (50mg/kg ip) and carotid artery was cannulated for recording blood pressure. JBF was recorded by laser Doppler flow meter. Joint vascular resistance (JVR) was calculated by dividing arterial blood pressure by JBF. Results: Based on Ang II dose/ response curve of joint blood vessels, the constrictor response was started from 10-12 M and reached to maximum at 10-5 M.Losartan completely inhibited this response with no vasodilation left behind, therefore the receptor subtypes are AT1. No evidence of presence of AT2 receptor subtype was observed in joint blood vessels. Conclusion: The comparison of the results of this study with a previous study on normal joints showed that the Ang II receptor subtypes did not change due to the process of acute inflammation. Keywords: Acute inflammation, Joint blood flow, Angiotensin II, Angiotensin receptor, rabbi

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

Abstract: 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 24 Newzealand white rabbits divided into three experimental and one control groups. Acute knee joint inflammation was produced by intraarticular injection of 0.5 ml of a 2% solution of carrageenan in knee joint. In the first group after 24 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 (10mg/kg) was administrated orally 2 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<0.01). 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<0.01). Conclusion: NO plays a role in the regulation of joint vascular tone and modulates theAT1receptor 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 AT1 receptors. Keywords: Angiotensin II, Nitric oxide, Reactive oxygen species , acute inflammation, Carragenan, knee joint, Rabbi