Background: Previous study has demonstrated an arterial inflammatory response in aortic tissues in several hypertensive models which can not be fully explained by hemodynamic forces. This study sought to investigate the effect of angiotensin II (Ang II)and its subtype-1 receptor blocker Losartan on the chemokine expression of monocyte chemoattractant protein-1(MCP-1) in aortic tissues of acute stage of 2-kidney-1-clip (2K1C) hypertensive rats.
Methods: 2K1C renovascular hypertension was produced in male Wistar-Kyoto(WKY) rats by placing a silver clip with an internal diameter of 0.2 mm around the left renal artery. The MCP-1 mRNA on aortic wall was detected by in situ hybridization and reverse transcription-polymerase chain reaction(RT-PCR); the levels of Ang II in plasma and aorta were determined by radioimmunoassay. The concentration of MCP-1 in supernatant of cultured endothelial cells (ECV-304) was measured by ELISA.
Results: No MCP-1 was exhibited in aortic wall of normotensive rats both by RT-PCR and in situ hybridization; it would be expressed on the aortic wall of rats in 7 days after 2K1C hypertensive model was formed, especially in intima. The expression of MCP-1 in aortic wall was increased with the duration of hypertension and correlated with local Ang II activity (r=0.594, P=0.02) other than those in plasma, it was decreased obviously after being treated by Losartan for 28 days (optical density of MCP-1/GAPDH ratio: 0, 0.58+/-0.10, 1.14+/-0.09, 1.52+/-0.20, 0.66+/-0.07, respectively, P<0.01). Ang II had increased the expression of MCP-1 in endothelial cells; the highest levels had been performed at 1x10(-7)mol/l Ang II or after 4 h, respectively; and losartan markedly reduced the expression of MCP-1.
Conclusions: The expression of MCP-1 significantly increases in aortic tissues of the acute stage 2K1C hypertensive rats and is decreased markedly by treatment of losartan. These findings imply Ang II may be involved in facilitating MCP-1 production in hypertension, and may provide a molecular link between hypertension and the development of atherosclerosis.