Hypercholesterolemia (HC) is characterized by increased circulating 8-epi-prostaglandin-F2α (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·min-1 or isoprostane (1 μg·kg-1·min-1). 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.
|Original language||English (US)|
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|Issue number||2 52-2|
|State||Published - 2002|
- Glomerular filtration rate
ASJC Scopus subject areas
- Physiology (medical)