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Angiotensin AT1 receptor antagonists exert anti-inflammatory effects in spontaneously hypertensive rats
1Department of Cardiology, Shanghai First People's Hospital, Jiaotong University, Shanghai, China.
Insights
Angiotensin AT1 receptor antagonists reduce inflammation in blood vessels by inhibiting monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2). This action may involve the PI3K/Akt pathway, offering new therapeutic insights.
Area of Science:
- Cardiovascular Pharmacology
- Immunology
- Molecular Biology
Background:
- Angiotensin AT1 receptor antagonists primarily lower blood pressure.
- These antagonists also possess anti-inflammatory properties in the cardiovascular system.
- The precise mechanisms behind these anti-inflammatory effects are not fully understood.
Purpose of the Study:
- To investigate the inhibitory effects of AT1 antagonists on monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2).
- To explore these effects in rat monocytes and aortas.
Main Methods:
- Spontaneous hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were used.
- SHRs were treated with losartan or telmisartan.
- Systolic blood pressure, aortic macrophage infiltration, MCP-1/CCR2 expression, and Akt phosphorylation were assessed.
Main Results:
- AT1 antagonists significantly reduced macrophage infiltration in the aortic wall of SHRs.
- Expression of MCP-1 and CCR2 in the aorta and monocytes was attenuated by AT1 antagonists.
- AT1 antagonists inhibited Akt phosphorylation in monocytes.
Conclusions:
- AT1 antagonism effectively inhibits inflammation in the vessel wall.
- The PI3K/Akt pathway may play a role in how AT1 antagonists modulate the MCP-1/CCR2 system.
Background And Purpose:
Although the main therapeutic effect of angiotensin AT1 receptor antagonists is to decrease blood pressure, they also exert anti-inflammatory effects in the cardiovascular system. However, the underlying mechanisms remain unclear. We investigated the inhibitory effect of AT1 antagonists on the chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2) in rat monocytes and aortas.
Experimental Approach:
Spontaneous hypertensive rats (SHRs) were treated with the AT1 antagonists losartan or telmisartan for 4 weeks, and Wistar-Kyoto rats (WKYs) were used as normotensive controls. Systolic arterial pressure was measured, and the number of macrophages in the aortic vessel wall was assessed by anti-ED-1 antibody immunolabelling.
Key Results:
Compared with WKYs, SHRs showed significantly increased ED-1 positive macrophages in the aortic wall, which were decreased after high doses of losartan or telmisartan. Low doses of losartan did not improve blood pressure significantly as did the high doses, but markedly decreased macrophage infiltration in the vessel wall. AT1 antagonists, particularly at high doses, improved aortic remodeling in SHR. At the molecular level, AT1 antagonists attenuated the expression of MCP-1 and CCR2 in the aorta and peripheral blood monocytes and lowered the serum level of MCP-1. In addition, Western blotting showed that AT1 antagonists inhibited the phosphorylation of Akt in mouse monocytes.
Conclusions And Implications:
AT1 antagonism inhibited vessel wall inflammation and inhibition of PI3K/Akt may be involved in the modulation of the MCP-1/CCR2 system by AT1 antagonists in SHRs.
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