Abstract P387: Depletion of Perivascular Macrophages in the Brain Delays Blood Pressure Elevation in Angiotensin II-salt Hypertensive Rats

Abstract

Objectives: Perivascular macrophages in the cerebrospinal fluid (CSF) are immune surveillance cells in the brain. Increase in angiotensin II (Ang II) in the periphery gradually produces neurogenic hypertension which is associated with brain inflammation. However, little is known on the role of perivascular macrophages in the CSF on neurogenic hypertension. We hypothesized that perivascular macrophages in the CSF have an important role in the development of neurogenic hypertension by relaying and amplifying excess peripheral Ang II signals to brain parenchyma. Methods: Sprague-Dawley rats had surgery to instrument radio telemetric pressure transducers to abdominal aorta. Following a one-week recovery period, the rats had surgery to implant either saline or Ang II filled osmotic minipump subcutaneously and received intracerebroventricular (icv) injection of either control liposome or clodronate liposome. The clodronate liposome is a drug that selectively induces apoptosis to macrophages which have liposome phagocytic activity. After the surgery, all rats were provided high-salt diet (2.0% NaCl). Blood pressure of rats was recorded three times a week for 2 weeks. Different set of rats had hexamethonium challenge test to evaluate sympathetic tone in 7 or 9 day after initiation of the infusions. Results: Rats that received Ang II infusion with control icv (n=7) gradually increased mean arterial pressure (MAP) compared with rats that received saline infusion (n=5) and reached significant increase in 6 days after the initiation of infusions. Rats that received Ang II infusion with clodronate icv (n=6) had delayed increase in MAP and reached significant increase in 10 days and had significantly lower MAP (91±4 mmHg) compared with rats that received Ang II infusion with control icv (111±4 mmHg) in day 8. Peak depressor response to hexamethonium was increased only in rats that received Ang II infusion with control icv when compared with saline infused rats examined in 7 or 9 days after initiation of the infusions. Conclusion: Perivascular macrophages in the CSF may have important role in the development of angiotensin II-salt neurogenic hypertension.