Brain Perivascular Macrophages and Central Sympathetic Activation After Myocardial Infarction

Abstract

Heart failure (HF) is characterized by an enhanced neurohumoral drive, which is currently the major therapeutic target.1,2 Recent studies to explore the mechanisms involved in central sympathetic outflow in HF have revealed several candidate mechanisms, such as reduced NO activity, increased oxidative stress, and activation of the brain angiotensin-aldosterone system.1–3 Interactions between these complex factors may also induce transcription factor alterations and increase sympathetic nervous system activity. The article in the present issue of Hypertension by Yu et al4 describes a very interesting concept that peripheral macrophages mediate central sympathetic activation after myocardial infarction (MI). Kang et al5 suggested previously that cyclooxygenase-2 (COX-2) and the subsequently generated prostaglandin E2 (PGE2), which crosses the blood-brain barrier, increase sympathetic activity. In this study, Yu et al4 injected clodronate liposomes intracerebroventricularly into rats 24 hours after inducing acute MI to selectively eliminate MI-induced brain perivascular macrophages. Because the effects of the clodronate liposomes peak ≈1 week after injection, COX-2 immunoreactivity in perivascular macrophages and COX-2 mRNA and protein levels were evaluated 1 week later. Perivascular macrophages in the blood-brain barrier were successfully eliminated in rats treated with clodronate liposomes; as a result, COX-2 immunoreactivity was not observed, and …