Anti-Inflammatory Effect Of Angiotensin Receptor 1 Blockers (ARBS) And Its Mechanism

Objective: To observe ARBs induce the anti-inflammatory reaction on vessel, protection effect on target organs and the regulated effect of MCP-1/CCR2 pathway in Spontaneous Hypertensive Rats (SHR), and discuss the possible mechanism of MCP-1/CCR2 pathway in primary hypertension.Methods: Twenty-four SHR were randomly divided into Hypertensive Control Group (HC), Low dose Losartan Group (LL), High dose Losartan Group (HL), and Telmisartan Group (T), and six Wistar Kyoto Rats (WKY) were treated as Normal Control Group (NC). The animals were orally administered drugs for four weeks: LL Group: 5 mg?kg-1?d-1, HL Group and T Group: 30 mg?kg-1?d-1, HC Group and NC Group received distilled water. The number of macrophages infiltrated into thoracic aorta was tested by ED-1 immunohistochemistory. To evaluate the media and fibrosis of rats'thoracic aorta, the sections were stained by hematoxylin-and-eosin or Masson-trichrome. The concentration of MCP-1 protein in serum was tested by ELISA, the chemotaxis ability of mononuclear cells in peripheral circulation to MCP-1 was tested by chemotaxis assay, and the expression of MCP-1mRNA and CCR2mRNA in heart, kidney and thoracic aorta by RT-PCR.Results: Compared with NC Group, in HC Group, ED-1 positive cells in the wall of thoracic aorta (P<0.01), Left ventricular mass/body weight (LVM/BW) (P<0.05), Medial thickness / Lumen of the aorta vessel and the aortic perivascular fibrosis ratio (PVFR) were significantly increased, respectively (P<0.01, respectively). The protein level of MCP-1 in serum was improved (P<0.01). The chemotaxis of mononuclear cells in peripheral circulation to MCP-1 was obviously enhanced (P<0.01) as well as the expression of MCP-1, CCR2 in heart, kidney and thoracic aorta(P<0.01, respectively). Compared with HC Group, the ED-1 positive cells in the wall of thoracic aorta , The LVM/BW (HL compared with HC, P<0.01; T compared with HC, P<0.05), IMT/D and PVFR were attenuated in HL and T Group ( The blood pressure was significantly decreased in these groups compared with HC Group ) (P<0.01, respectively) as well as the chemotaxis of mononuclear cells in peripheral circulation to MCP-1 (P<0.01) and the expression of MCP-1 and CCR2 in tissues and circulation (P<0.01, respectively), meanwhile low dose of Losartan can exert the equal effects (P<0.01, respectively) without decreasing the blood pressure except inhibiting the hypertrophy of LV and vascular media .Conclusion: MCP-1/CCR2 may be one of the important mechanisms in causing inflammatory reaction and target organs damage in primary hypertension. ARBs may exert the effect of anti-inflammatory reaction and protect target organs via inhibiting MCP-1/CCR2 pathway independent of pressure decreased.