Improvement in middle cerebral artery structure and endothelial function in stroke-prone spontaneously hypertensive rats after macrophage depletion

Paulo W. Pires, Saavia S. Girgla, Jonathon L. Mcclain, Norbert E. Kaminski, Nico van Rooijen, Anne M. Dorrance

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)650-661
Number of pages12
JournalMicrocirculation
Volume20
Issue number7
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Endothelium-dependent vasodilation
  • Hypertension
  • Liposome-encapsulated clodronate
  • Middle cerebral artery
  • Vascular remodeling

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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