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An activation of neutrophils is present in high-risk individuals, shown by the enhanced production of IL-8, and increased ROS generation. The 4-week statin treatment is able to reduce the cell capability to produce IL-8, and to decrease chemotaxis, thus affecting the proinflammatory properties of PMNs.

Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments. The blood pressure reduction during drug assumption could not account for the pain sensitivity changes observed. The latter may be due to a specific pharmacodynamic mechanism mediated through angiotensin II AT1 receptors.

Statins may directly interfere with the effects of angiotensin (Ang) II, which is a key player in the pathogenesis of atherosclerosis (ATH). Ang II promotes a wide array of detrimental processes including a prominent proinflammatory effect, increasingly regarded as a target for therapeutic intervention. Because the proinflammatory effects of Ang II are exerted mainly through the activation of Ang II type 1 receptors (AT1Rs) the present study was devised to investigate by means of real-time polymerase chain reaction (PCR) and flow cytometry techniques the expression of such receptors on circulating polymorphonuclear leukocytes (PMNs) from subjects at high risk for vascular events before and during treatment with simvastatin and in sex- and age-matched healthy controls. In vitro experiments were also performed to assess the ability of simvastatin to interfere with Ang II signaling in human PMNs. In comparison to controls, high-risk subjects had similar AT1R expression on the cell membranes but significantly higher AT1R messenger ribonucleic acid (mRNA) levels. Treatment of high-risk subjects with simvastatin for 30 days resulted in a reduction of AT1R mRNA down to the levels of cells from healthy subjects. In vitro, Ang II-induced activation of the guanosine triphosphate (GTP)-binding protein Rac 1 in human PMNs was inhibited by simvastatin. In conclusion, simvastatin induces downregulation of AT1R expression, interferes with Ang II activity in PMNs, and contributes to the antiinflammatory profile of statins that can explain the therapeutic effects of these drugs.

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