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Perivascular macrophages mediate endothelium dysfunction in the middle cerebral artery of hypertensive rats
Author(s) -
Pires Paulo Wagner,
Girgla Saavia Singh,
Lee McClain Jonathon,
VanRooijen Nico,
Dorrance Anne McLaren
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.888.7
Subject(s) - dilator , constriction , sodium nitroprusside , electrical impedance myography , medicine , nitric oxide , middle cerebral artery , vasodilation , cerebral arteries , endothelium , endothelial dysfunction , acetylcholine , endocrinology , cerebral circulation , vasoconstriction , anesthesia , ischemia
Hypertension increases macrophages (MΦ) around the cerebral arteries. These MΦ may release mediators that could modulate endothelial function. We hypothesized that MΦ depletion would improve middle cerebral artery (MCA) endothelial function in stroke‐prone spontaneously hypertensive rats (SHRSP). Liposome‐encapsulated clodronate (CLOD) was used to deplete MΦ, control rats received PBS containing liposomes; rats were treated from 6–12 weeks of age. Data are mean±SEM, PBS vs CLOD. Dilation data is shown for the highest concentration of the dilator. SHRSP+CLOD had less perivascular MΦ around the cerebral arteries (0.7±0.1 vs 0.3±0.1, n=5, p<0.01). Pressurized MCAs from SHRSP+CLOD showed improved dilation to ADP (change from baseline: 32.8±3.4 vs 50.8±9.7μm, n=6, p<0.05). Endothelial function was further assessed with acetylcholine (Ach)±N‐nitro‐L‐arginine methyl ester (L‐NAME) by wire myography (n=7). MCAs from SHRSP+CLOD had improved dilation to Ach (%KCl constriction: 64.8±5.0 vs 51.8±4.4, p<0.05), which was blunted by L‐NAME (%KCl constriction: 80.8±7.6 vs 79.8±5.0). Endothelium‐independent dilation to sodium nitroprusside was unchanged (%KCl constriction: 39.4±3.2 vs 43.1±2.1). These data suggest that perivascular MΦ might reduce endothelial nitric oxide generation in MCAs from SHRSP.