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Amelioration of Endothelial Dysfunction in Middle Cerebral Arteries (MCA) of Fawn‐Hooded Rats by Antioxidant Treatment and Chromosomal Substitution
Author(s) -
Weinberg Brian,
Lombard Julian H
Publication year - 2012
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.26.1_supplement.1098.13
Subject(s) - medicine , endocrinology , oxidative stress , cerebral arteries , endothelial dysfunction , introgression , reactive oxygen species , middle cerebral artery , superoxide dismutase , antioxidant , biology , colocalization , gene , biochemistry , microbiology and biotechnology , ischemia
The Fawn‐Hooded Hypertensive (FHH) rat is a genetic model of spontaneous high‐renin systemic hypertension and multiple other disorders. As such, it is important to gain an increased understanding of genetic factors controlling systemic vascular reactivity in this strain. We evaluated vascular function in isolated middle cerebral arteries (MCA) from 8–10 week old FHH rats and 3 consomic panels carrying Brown Norway (BN) chromosomes (1,5, and 13) shown to be important in regulating vascular reactivity. All rats were maintained on a low salt (0.4% NaCl) diet since weaning. MCA's from FHH failed to dilate to acetylcholine (ACh, 10 −10 M to 10 −5 M). Introgression of BN chromosomes 1 and 13 partially restored ACh‐induced dilation. Introgression of BN chromosome 5 (carrying CYP4A alleles), acute addition of the superoxide (O 2 • − ) scavenger tempol, and scavenging of mitochondrial O 2 • − with mito‐Q caused a dramatic restoration of ACh‐induced vascular relaxation. Mitochondrial O 2 • − levels (evaluated with the specific fluorescent probe MitoSOX) were significantly higher in MCA of FHH vs. the well characterized Sprague‐Dawley rat. These findings indicate that chronic elevations in oxidant stress disrupt cerebral vascular reactivity in FHH rats, and that different genes and chromosomes are likely to contribute to vascular dysregulation in different forms of hypertension. (NIH #HL‐65289; #HL‐72920, #HL‐92026).