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in normal and hypercholesterolemic pigs
Department of Internal Medicine, Divisions of 1 Hypertension and 2 Cardiovascular Diseases, and the 3 Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905
Hypercholesterolemia (HC) is
characterized by increased circulating
8-epi-prostaglandin-F2
(isoprostane), a
vasoconstrictor, marker, and mediator of increased oxidative stress,
whose vascular effects might be augmented in HC. Anesthetized pigs were
studied in vivo with electron beam computed tomography after a 12-wk
normal (n = 8) or HC (n = 8) diet. Mean
arterial pressure (MAP), single-kidney perfusion, and glomerular
filtration rate (GFR) were quantified before and during unilateral
intrarenal infusions of U46619 (10 ng · kg
1 · min1) or
isoprostane (1 µg · kg1 · min1). Basal
renal perfusion and function were similar, and isoprostane infusion
elevated its systemic levels similarly in normal and HC (333 ± 89 vs. 366 ± 48 pg/ml, respectively, P < 0.01 vs.
baseline). Both drugs markedly and comparably decreased cortical
perfusion and GFR in both groups, whereas medullary perfusion decreased significantly only in HC. Moreover, MAP increased significantly only in
HC (+9 ± 3 and +11 ± 3 mmHg, respectively, P
0.05). Hence, in HC, renal functional responses to high-dose
isoprostane are largely similar to normal, but the systemic circulation
exhibits augmented sensitivity to pathophysiological levels of
isoprostane and U46619, which may potentially play a role in
development of hypertension and vascular injury associated with
increased oxidative stress.
hypercholesterolemia; glomerular filtration rate
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