title: Improvement in middle cerebral artery structure and endothelial function in stroke-prone spontaneously hypertensive rats after macrophage depletion.
abstract: BACKGROUND
  Inflammation is involved in the pathogenesis of hypertension. Hypertensive animals have an increased number of perivascular macrophages in cerebral arteries. Macrophages might be involved in remodeling of the cerebral vasculature. We hypothesized that peripheral macrophage depletion would improve MCA structure and function in hypertensive rats.
  
  
  METHODS
  For macrophage depletion, six-week-old stroke-prone spontaneously hypertensive rats (SHRSP) were treated with CLOD, 10 mL/kg every three or four days, i.p., or vehicle (PBS lipo). MCA structure and function were analyzed by pressure and wire myography.
  
  
  RESULTS
  Blood pressure was not affected by CLOD. The number of perivascular CD163-positive cells per microscopic field was reduced in the brain of SHRSP+CLOD. CLOD treatment caused an improvement in endothelium-dependent dilation after intralumenal perfusion of ADP and incubation with Ach. Inhibition of NO production blunted the Ach response, and endothelium-independent dilation was not altered. At an intralumenal pressure of 80 mmHg, MCA from SHRSP+CLOD showed increased lumen diameter, decreased wall thickness, and wall-to-lumen ratio. Cross-sectional area of pial arterioles from SHRSP+CLOD was higher than PBS lipo.
  
  
  CONCLUSIONS
  These results suggest that macrophage depletion attenuates MCA remodeling and improves MCA endothelial function in SHRSP.
authors: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA.
authors: Paulo W
authors: PW
authors: Pires
authors: Saavia S
authors: SS
authors: Girgla
authors: Jonathon L
authors: JL
authors: McClain
authors: Norbert E
authors: NE
authors: Kaminski
authors: Nico
authors: N
authors: van Rooijen
authors: Anne M
authors: AM
authors: Dorrance
mesh_terms: D000818:Animals; D001794:Blood Pressure; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D004002:Clodronic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008264:Macrophages; D008297:Male; D020768:Middle Cerebral Artery / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation
chemical_list: D050071:Bone Density Conservation Agents; D004002:Clodronic Acid
keywords: endothelium-dependent vasodilation; hypertension; liposome-encapsulated clodronate; middle cerebral artery; vascular remodeling
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