Simvastatin Reduces Pressor Response to Centrally Administered Angiotensin II

Abstract

Angiotensin II (Ang II) plays a pivotal role in regulation of the circulatory system. Activation of angiotensin type 1 (AT1) receptors in several brain regions leads to an increase in blood pressure. Accumulating data suggest that statins affect the peripheral action of Ang II; however, their central effects are poorly recognized. The study was aimed to determine whether simvastatin interferes with the brain angiotensin system in rats. Twelve-week-old, Sprague-Dawley rats were divided into two groups. Untreated group was maintained on tap water, whereas simvastatin group received water containing simvastatin for the following 12 weeks. Later, both groups were subjected to experiments in which mean arterial blood pressure (MABP) and heart rate (HR) were recorded during baseline conditions and after intracerebroventricular (ICV) infusion of either saline, Ang II, or losartan. ICV infusion of Ang II elicited a significant increase in MABP in both groups. However, the pressor response in the simvastatin group was significantly smaller than that in the untreated group. There was no significant change in MABP after ICV infusion of saline or losartan. ICV infusion of Ang II elicited a significant increase in HR in the untreated group but not in the simvastatin group. There was no significant change in HR after ICV infusion of saline or losartan. The results show that simvastatin reduces the pressor response to ICV-infused Ang II in rats. This implies that statins may affect the central regulation of the circulatory system, especially when the brain angiotensin system is stimulated.