Vascular responses in vivo to 8-epi PGF2 in normal and hypercholesterolemic pigs

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-week 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 intra-renal infusions of U46619 (10ng/kg/min) or Isoprostane (1μg/kg/min). 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, while medullary perfusion decreased significantly only in HC. Moreover, MAP increased significantly only in HC (+9±3 and +11±3mmHg, 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.