Vascular responses in vivo to 8-epi PGF(2alpha) in normal and hypercholesterolemic pigs.
Hypercholesterolemia (HC) is characterized by increased circulating 8-epi-prostaglandin-F(2alpha) (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 x kg(-1) x min(-1)) or isoprostane (1 microg x kg(-1) x 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<or= 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.
Department of Internal Medicine, Division of Hypertension, Mayo Clinic, Rochester, Minnesota 55905, USA.
James D
JD
Krier
Martin
M
Rodriguez-Porcel
Patricia J M
PJ
Best
J Carlos
JC
Romero
Amir
A
Lerman
Lilach O
LO
Lerman
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D028441:F2-Isoprostanes / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006937:Hypercholesterolemia / Q000503:physiopathology*; D028421:Isoprostanes / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014057:Tomography, X-Ray Computed; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects* / Q000503:physiopathology
D028441:F2-Isoprostanes; D028421:Isoprostanes; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost