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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
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ABSTRACT |
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 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
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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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INTRODUCTION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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HYPERCHOLESTEROLEMIA
(HC) is a common cardiovascular risk factor that impairs vascular
function before development of overt atherosclerosis. One of the
mechanisms by which HC may induce functional and structural alterations
is instigation of reactive oxygen species formation, or increased
oxidative stress, in association with lipid peroxidation
(26). A recently discovered series of prostaglandin (PG)
F2-like compounds, 8-epi PGF2
(isoprostane), are produced in vivo by nonenzymatic free radical
catalyzed peroxidation of arachidonic acid (26), as may
occur during oxidation of low-density lipoprotein (LDL). Plasma levels
of isoprostane are elevated in HC humans (6, 29) and pigs
(3, 33, 42) and represent novel markers of endogenous
lipid peroxidation and oxidant status in vivo (30).
Moreover, isoprostane can exert potent biological activity such as
vasoconstriction (18), and it has been proposed to mediate
oxidant injury (30) and contribute to the vascular pathobiology associated with atherosclerosis (24).
The kidney is susceptible to abnormal lipid metabolism, which may modify and accelerate glomerular and vascular damage. We previously showed that swine diet-induced HC was associated with impaired functional responses to challenge of the renal vasculature in vitro (36, 37) and renal perfusion in vivo (8, 32). Imbalance between vasodilators and vasoconstrictors, increased oxidative stress (34), or enhanced response to vasoconstrictors like isoprostane (8) may contribute to functional and eventually structural vascular and renal injury in HC. However, it is yet unknown whether the HC kidney exhibits abnormal responses to isoprostane.
Electron beam computed tomography (EBCT) is an ultrafast scanner that allows reliable, noninvasive quantifications of single-kidney regional perfusion and glomerular filtration rate (GFR) (17). This technique thus allows a unique opportunity to study the direct effect of isoprostane on the in vivo intact pig kidneys. Therefore, the present study was designed to examine whether in HC pigs intrarenal perfusion and function show differential responses to isoprostane compared with normal, and furthermore, whether such responses were selective to isoprostane or shared by a thromboxane (Tx) receptor agonist.
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METHODS |
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INTRODUCTION
METHODS
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DISCUSSION
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This study was performed according to Institutional Animal Care and Use guidelines. Domestic female pigs (55-65 kg) were studied with EBCT after 12 wk of either a normal (n = 8) or HC diet (n = 8) consisting of 2% cholesterol (Harlan Teklad, Madison, WI) (8).
EBCT studies.
On the day of the EBCT study, each animal was anesthetized with
0.5 g of intramuscular ketamine and xylazine, intubated, and mechanically ventilated with room air. Anesthesia was maintained with a
mixture of ketamine (0.2 mg · kg1 · min1) and
xylazine (0.03 mg · kg1 · min1) in normal
saline, and it was administered via an ear vein cannula at a rate of
0.05 ml · kg1 · min1. Under
sterile conditions and fluoroscopic guidance, an 8F arterial guide was
inserted in the left carotid artery and advanced to the abdominal
aorta; a tracker catheter was advanced within the guide and positioned
in the midsection of the left renal artery. The arterial guide was
maintained at a level above the scanning plane and served for
monitoring mean arterial pressure (MAP) throughout the experiment. A
pigtail catheter was advanced through a jugular vascular sheath and
positioned in the superior vena cava or right atrium for subsequent
contrast media injections, and another suprapubic catheter was placed
in the urinary bladder for urine collection. Saline infusion (3-4
ml/min) was initiated into a side arm of the venous vascular sheath,
and electrocardiogram leads served for monitoring heart rate.
1 · min1)
(5) or isoprostane (1 µg · kg1 · min1)
(26, 38). Intrarenal saline infusion was resumed between studies.
Urine was collected for 5 min before each EBCT study for determination
of urinary flow rate (using a graduated cylinder) and creatinine
(spectrophotometry) excretion. A blood sample was collected from the
superior vena cava in the middle of the baseline and isoprostane
infusion collection periods for measurement of isoprostane. The sample
obtained at baseline was also used to measure lipid profile (Roche,
Nutley, NJ), thiobarbituric acid-reactive substances (TBARS) using the
colorimetric method (21), electrolytes (flame photometry),
and plasma renin activity (PRA; New England Nuclear, Boston, MA).
PGF2-isoprostanes were measured in blood samples that
were collected in EDTA tubes, separated, and the plasma stored at
80°C until the time of assay. The total levels of isoprostane were
measured with an enzyme immunoassay kit (EIA, Cayman) for 8-iso-PGF2 (2), as previously described
(12, 21). Briefly, before the enzyme immunoassay, an
alkaline hydrolysis was used, and plasma samples were purified by
Sep-Pak C-18 columns (Milford, MA). The samples, tracer, and antiserum
were added to wells precoated with mouse monoclonal antibody, and the
plates were washed to remove all unbound reagents. Ellman's reagent
(containing the substrate to acetylcholinesterase) was added to the
wells. The intensity of the distinct yellow color produced by this
enzymatic reaction was determined using a spectrophotometer at 405 nm.
This assay has high accuracy as determined by a standard curve plotted using a four-parameter fit, with a correlation coefficient of 0.99 (4, 14). Standard solution concentrations (5-500
pg/tube) show 91.2 ± 0.6 to 26.7 ± 0.5% binding,
respectively, with a specificity of 98%. The interassay variability,
tested by running controls over an 18-mo period, is <10%
(4).
EBCT scanning sequence. Each EBCT study was performed during respiratory suspension at end expiration. With the use of localization scans, two midhilar tomographic levels of the left kidney were selected. For the study of renal perfusion and function, the kidney was scanned in the multislice flow mode (50 ms/image), resulting in two contiguous 8-mm thick midhilar sections. Forty consecutive scans (over 3 min) were initiated and performed at variable time intervals 4 s after a central venous bolus injection (0.5 ml/kg over 1 s) of the nonionic, low-osmolar contrast medium iopamidol (Isovue-370, Squibb Diagnostics, Princeton, NJ), as previously described (8, 17, 32). After completion of all studies, the pigs were euthanized with a lethal infusion of Sleepaway (Fort Dodge Laboratories, Fort Dodge, IA).
EBCT data analysis. All images were reconstructed on the EBCT workstation, transferred, and displayed on a Sun workstation. The densities of the aorta, cortex, medulla, and papilla were sampled after manually tracing these regions of interest. Time-density curves were generated for each region and fitted with extended gamma-variate curve fit, as previously described (17). Renal regional perfusion (ml/min per cm3 tissue) was then calculated as: 60 × vascular blood volume/mean transit time (17, 32). Normalized single-kidney GFR (ml/min per cm3 tissue) was calculated as: 60 × kidney volume × slope of the accumulation of contrast in the proximal tubule × mean transit time/area under the aortic input curve (17, 32).
Statistical analysis.
Results are means ± SE. Comparisons between experimental periods
were performed by paired Student's t-test, and between
groups using unpaired t-test, with the Bonferroni correction
for multiple comparisons. Statistical significance was determined at
P 0.05.
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RESULTS |
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Systemic parameters.
Total cholesterol levels were significantly higher in HC compared with
normal pigs (395 ± 60 vs. 67 ± 7 mg/dl, P < 0.001), as were LDL levels (P < 0.001). Plasma
TBARS were significantly higher in HC compared with normal (3.7 ± 0.1 vs. 3.2 ± 0.2 nmol/ml, P < 0.05), and total
plasma isoprostane tended to be elevated as well (123 ± 13 vs.
98 ± 13 pg/ml, P = 0.09). Basal MAP was significantly lower in HC pigs (Table 1),
whereas heart rate was similar. Plasma creatinine levels were
significantly higher in HC compared with normal (1.9 ± 0.1 vs.
1.6 ± 0.1 mg/dl, P < 0.05), whereas PRA was
similar in both groups (P = 0.2; Table 1).
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Renal hemodynamics and function.
Basal single-kidney perfusion and GFR were similar in normal and HC
pigs (Table 2). During intrarenal
infusion of either U46619 or isoprostane, the significant decreases in
GFR of the infused kidneys were comparable in normal (68 ± 9 and 35 ± 14%, respectively) and HC pigs (72 ± 8 and
49 ± 7%, respectively). Likewise, U46619 and isoprostane
induced similar reductions in regional renal perfusion in both groups.
In response to U46619 and isoprostane, cortical perfusion decreased in
both normal (by 73 ± 11 and 36 ± 13%, respectively)
and HC (by 77 ± 7 and 55 ± 9%, respectively; Table 2)
pigs. U46619 induced significant reductions in medullary perfusion in
both normal and HC (55 ± 17 and 67 ± 12%,
respectively), but a decrease in medullary perfusion in response to
isoprostane observed in HC (47 ± 11%, P = 0.004) has not reached statistical significance in normal pigs
(31 ± 17%, P = 0.07; Table 2). Papillary
perfusion decreased significantly in response to U46619 in normal and
HC pigs (44 ± 11 and 54 ± 23%, respectively), whereas
isoprostane did not significantly reduce papillary perfusion in either
normal or HC pigs (27 ± 17 and 12 ± 12%, respectively;
Table 2).
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DISCUSSION |
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ABSTRACT
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This study demonstrates that intrarenal infusion of high-dose isoprostane decreases cortical perfusion and GFR similarly in normal and HC pigs but may induce a greater decline in medullary perfusion in HC. In addition, a greater increase in blood pressure in HC in response to isoprostane may imply increased propensity for systemic vasoconstriction and augmented sensitivity to pathophysiological levels of isoprostane. Similarly, augmented sensitivity was observed in response to the Tx receptor agonist U46619, suggesting that these abnormalities were not selective to isoprostane. These effects may potentially play a role in development of hypertension and in vascular injury associated with HC and increased lipid peroxidation.
HC is characterized by attenuated vasodilatory responses and augmented propensity for vasoconstriction (11, 13), as well as by an increase in circulating levels of isoprostane (3, 33, 42), a vasoconstrictor and marker of increased oxidative stress in vivo. In the current study, isoprostane levels in HC pigs tended to increase, and the levels of TBARS, additional markers of increased oxidative stress, were significantly elevated. In addition, in our HC model, systemic LDL oxidizability is markedly increased and systemic endogenous antioxidant defenses markedly decreased (32, 33, 37), indicating increased oxidative stress. We previously showed in the pig model that HC was also associated with an enhanced coronary vasoconstriction response to isoprostane in vitro (43). However, the effect of isoprostane on the systemic circulation in HC in vivo has not been demonstrated. In the renal circulation, HC also induces abnormal vascular responses to challenge, both in vivo (8, 32) and in vitro (36), likely related to increased oxidative stress and lipid peroxidation (32, 37). However, renal responsiveness to isoprostane in HC, or its potential involvement in renal functional abnormalities, has not been evaluated.
The potent vasoconstrictor effect of isoprostane is mediated via a dose-dependent and reversible (39) interaction with vascular Tx/endoperoxide receptor. However, the subsequent downstream signaling mechanisms triggered by isoprostane are largely different from those activated by U46619 (19, 20) and may mediate their specific proatherogenic effects (9, 20). Distinct isoprostane receptor sites on vascular smooth muscle cells may also account for their marked potency (10). Furthermore, unlike primary PGs, which are rapidly metabolized to inactive products, isoprostane circulates in plasma (28) and may hence induce or amplify concurrent pathological processes. Therefore, in HC and atherosclerosis, isoprostane might conceivably have selective and distinct effects and participate in disease progression.
Our study underscores the striking sensitivity of the intact kidney to the direct effects of vasoconstrictor PG (41). Intrarenal infusion of isoprostane or U46619 in both normal and HC pigs induced marked cortical vasoconstriction and decrease in GFR, comparable to the decrease in GFR and renal blood flow previously observed in normal animals in response to similar doses of isoprostane (26) or U46619 (5). Interestingly, most of the functional renal responses to both U46619 and isoprostane were similar in normal and HC pigs. The exception was medullary perfusion that decreased slightly more in HC, possibly reflecting vulnerability of the medullary circulatory to injury involving increased oxidative stress. Indeed, to demonstrate their vasoconstrictor effect on the kidney, the conventional dose of isoprostane infused in the current as well as in previous studies (26, 38) was higher than the basal circulating level that we observed. However, its systemic (31) and intrarenal production is markedly elevated under inflammatory (16) and oxidative stress (23) conditions and may approach the infused concentration. Furthermore, the marked vasoconstriction induced by intrarenal infusion might have conceivably masked subtle differential sensitivity to lower circulating levels of the drugs.
This postulation may be supported by the systemic effects of U46619 and isoprostane observed in HC, implying augmented vascular sensitivity to the drugs. In both groups, intrarenal systemic spillover during isoprostane infusion likely increased their circulating levels similarly, but an increase in MAP and decrease in heart rate were observed in HC alone. Speculatively, the increase in MAP in HC might have led to the small increase in urinary flow rate, whereas an overall decrease in creatinine excretion rate might have resulted from a concurrent decrease in GFR of the contralateral kidney exposed to pathophysiological circulating levels of the drugs. The reason for the slightly higher basal creatinine excretion rate observed in HC pigs is unclear.
Increased sensitivity to the pressor effects of U46619 has been previously observed in physiological conditions like salt loading and may result from increased abundance and activation of the renal TxA2/PGH2 receptor (40). In HC, enhanced sensitivity to vasoconstrictor PG may be related to endothelial injury, increased production of TxA2 (1), or interaction with coexisting vasoconstrictors (21). The unchanged PRA during infusions (in fact, slight decrease in HC during infusion of U46619) argues against significant involvement of the systemic renin-angiotensin system. On the other hand, decreased bioavailability of nitric oxide and increased production of superoxide, two conditions that characterize HC, enhance activation of the TxA2 receptor and vasoconstriction responses to U46619 in isolated renal afferent arterioles (35).
Notably, despite the potential vasoconstrictor impact of isoprostane and its increased circulating levels in HC, basal MAP in this group was lower than normal (1). HC pigs exhibit enhanced propensity for diuresis and natriuresis in response to challenge (8, 32) and attenuated development of renovascular hypertension (32), possibly related to intrarenal proinflammatory changes (8). Nevertheless, the increase in MAP in HC may also reflect augmented vascular sensitivity to additional more subtle effects, such as platelet activation, vascular remodeling, or nephropathy (23). Although basal isoprostane level in HC was lower than the level that induced the increase in MAP during infusion, the augmented vascular sensitivity in HC may facilitate development of hypertension and vascular injury during more prolonged or comorbid conditions associated with increased oxidative stress. Elevated circulating isoprostane levels similar to those observed during isoprostane infusion can be observed in pathophysiological human conditions such as preeclampsia (22), coronary reperfusion (15), cirrhosis (27), smoking (25), and diabetes (7). HC may hypothetically act in concert with coexisting pathophysiological mechanisms and facilitate disease progression (32), development of hypertension, and clustering of risk factors. Hence, a potential role for isoprostane as endogenous mediator of hypertension and vascular injury under such conditions cannot be ruled out.
In summary, our study demonstrates an increase in arterial pressure in HC pigs in response to pathophysiological systemic levels of isoprostane and U46619, supporting a potential role for vasoconstrictor PG in development of hypertension in disease states associated with increased oxidative stress and comorbid or chronic conditions. The response of the HC kidney to high-dose infusion was comparable to normal, although medullary perfusion may show enhanced response to isoprostane. Furthermore, the similar degree of vascular response to isoprostane compared with U46619 does not rule out activation of additional downstream pathogenic mechanisms by isoprostane. These effects may potentially play a role in vascular injury associated with abnormal lipid metabolism and increased oxidative stress.
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ACKNOWLEDGEMENTS |
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The authors are grateful to the staff of the EBCT for the technical assistance with performance of the experiments.
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FOOTNOTES |
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This study was supported by Grant HL-63282 from the National Institutes of Health and Grant 99603367 from the Northland Affiliate of the American Heart Association. This work has been presented in part at the 16th Annual Scientific Meeting of the American Society of Hypertension in May 2001.
Address for reprint requests and other correspondence: L. O. Lerman, Division of Hypertension, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 (E-mail: Lerman.Lilach{at}Mayo.Edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
May 6, 2002;10.1152/ajpregu.00602.2001
Received 3 October 2001; accepted in final form 16 April 2002.
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REFERENCES |
|---|
|
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Bank, N,
and
Aynedjian HS.
Role of thromboxane in impaired renal vasodilatation response to acetylcholine in hypercholesterolemic rats.
J Clin Invest
89:
1636-1642,
1992[ISI][Medline].
2.
Basu, S.
Radioimmunoassay of 8-iso-prostaglandin F2: an index for oxidative injury via free radical catalysed lipid peroxidation.
Prostaglandins Leukot Essent Fatty Acids
58:
319-325,
1998[ISI][Medline].
3.
Best, PJM,
Lerman LO,
Romero JC,
Holmes DR, Jr,
and
Lerman A.
Coronary endothelial function is preserved with chronic endothelin receptor antagonism in experimental hypercholesterolemia in vitro.
Arterioscler Thromb Vasc Biol
19:
2769-2775,
1999
4.
Bolterman, R,
Haas J,
Stulak JM,
and
Romero JC.
Determination of plasma isoprostanes by enzyme immunoassay in pigs. A reliable and sensitive assay (Abstract).
Hypertension
33:
1068,
1999.
5.
Cirino, M,
Morton H,
MacDonald C,
Hadden J,
and
Ford-Hutchinson AW.
Thromboxane A2 and prostaglandin endoperoxide analogue effects on porcine renal blood flow.
Am J Physiol Renal Fluid Electrolyte Physiol
258:
F109-F114,
1990
6.
Davi, G,
Alessandrini P,
Mezzetti A,
Minotti G,
Bucciarelli T,
Costantini F,
Cipollone F,
Bon GB,
Ciabattoni G,
and
Patrono C.
In vivo formation of 8-Epi-prostaglandin F2
is increased in hypercholesterolemia.
Arterioscler Thromb
17:
3230-3235,
1997
7.
Davi, G,
Ciabattoni G,
Consoli A,
Mezzetti A,
Falco A,
Santarone S,
Pennese E,
Vitacolonna E,
Bucciarelli T,
Costantini F,
Capani F,
and
Patrono C.
In vivo formation of 8-iso-prostaglandin f2 and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation.
Circulation
99:
224-229,
1999
8.
Feldstein, A,
Krier JD,
Hershman Sarafov M,
Lerman A,
Best PJM,
Wilson SH,
and
Lerman LO.
In vivo renal vascular and tubular function in experimental hypercholesterolemia.
Hypertension
34:
859-864,
1999
9.
Fontana, L,
Giagulli C,
Minuz P,
Lechi A,
and
Laudanna C.
8-Iso-PGF2 induces 
2-integrin-mediated rapid adhesion of human polymorphonuclear neutrophils: a link between oxidative stress and ischemia/reperfusion injury.
Arterioscler Thromb Vasc Biol
21:
55-60,
2001
10.
Fukunaga, M,
Makita N,
Roberts LJD,
Morrow JD,
Takahashi K,
and
Badr KF.
Evidence for the existence of F2-isoprostane receptors on rat vascular smooth muscle cells.
Am J Physiol Cell Physiol
264:
C1619-C1624,
1993
11.
Galle, J,
Bassenge E,
and
Busse R.
Oxidized low density lipoproteins potentiate vasoconstrictions to various agonists by direct interaction with vascular smooth muscle.
Circ Res
66:
1287-1293,
1990
12.
Haas, JA,
Krier JD,
Bolterman RJ,
Juncos LA,
and
Romero JC.
Low-dose angiotensin II increases free isoprostane levels in plasma.
Hypertension
34:
983-986,
1999
13.
Heistad, DD,
Armstrong ML,
Marcus ML,
Piegors DJ,
and
Mark AL.
Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys.
Circ Res
54:
711-718,
1984
14.
Hoffman, SW,
Roof RL,
and
Stein DG.
A reliable and sensitive enzyme immunoassay method for measuring 8-isoprostaglandin F2: a marker for lipid peroxidation after experimental brain injury.
J Neurosci Methods
68:
133-136,
1996[ISI][Medline].
15.
Iuliano, L,
Pratico D,
Greco C,
Mangieri E,
Scibilia G,
FitzGerald GA,
and
Violi F.
Angioplasty increases coronary sinus F2-isoprostane formation: evidence for in vivo oxidative stress during PTCA.
J Am Coll Cardiol
37:
76-80,
2001
16.
Klein, T,
Neuhaus K,
Reutter F,
and
Nusing RM.
Generation of 8-epi-prostaglandin F(2) in isolated rat kidney glomeruli by a radical-independent mechanism.
Br J Pharmacol
133:
643-650,
2001[ISI][Medline].
17.
Krier, JD,
Ritman EL,
Bajzer Z,
Romero JC,
Lerman A,
and
Lerman LO.
Noninvasive measurement of concurrent, single-kidney perfusion, glomerular filtration, and tubular function.
Am J Physiol Renal Physiol
281:
F630-F638,
2001
18.
Kromer, BM,
and
Tippins JR.
Coronary artery constriction by the isoprostane 8-epi prostaglandin F2.
Br J Pharmacol
119:
1276-1280,
1996[ISI][Medline].
19.
Kunapuli, P,
Lawson JA,
Rokach JA,
Meinkoth JL,
and
FitzGerald GA.
Prostaglandin F2 (PGF2) and the isoprostane, 8,12-iso-isoprostane F2-III, induce cardiomyocyte hypertrophy. Differential activation of downstream signaling pathways.
J Biol Chem
273:
22442-22452,
1998
20.
Leitinger, N,
Huber J,
Rizza C,
Mechtcheriakova D,
Bochkov V,
Koshelnick Y,
Berliner JA,
and
Binder BR.
The isoprostane 8-iso-PGF2a stimulates endothelial cells to bind monocytes: difference to thromboxane-mediated endothelial activation.
FASEB J
15:
1254-1256,
2001
21.
Lerman, LO,
Nath KA,
Rodriguez-Porcel M,
Krier JD,
Schwartz RS,
Napoli C,
and
Romero JC.
Increased oxidative stress in experimental renovascular hypertension.
Hypertension
37:
541-546,
2001
22.
McKinney, ET,
Shouri R,
Hunt RS,
Ahokas RA,
and
Sibai BM.
Plasma, urinary, and salivary 8-epi-prostaglandin f2 levels in normotensive and preeclamptic pregnancies.
Am J Obstet Gynecol
183:
874-877,
2000[ISI][Medline].
23.
Montero, A,
Munger KA,
Khan RZ,
Valdivielso JM,
Morrow JD,
Guasch A,
Ziyadeh FN,
and
Badr KF.
F(2)-isoprostanes mediate high glucose-induced TGF- synthesis and glomerular proteinuria in experimental type I diabetes.
Kidney Int
58:
1963-1972,
2000[ISI][Medline].
24.
Moore, KP,
Darley-Usmar V,
Morrow J,
and
Roberts LJN
Formation of F2-isoprostanes during oxidation of human low density lipoprotein and plasma by peroxynitrite.
Circ Res
77:
335-341,
1995
25.
Morrow, JD,
Frei B,
Longmire AW,
Gaziano JM,
Lynch SM,
Shyr Y,
Strauss WE,
Oates JA,
and
Roberts LJ II.
Increase in circulating products of lipid peroxidation (F2- isoprostanes) in smokers. Smoking as a cause of oxidative damage.
N Engl J Med
332:
1198-1203,
1995
26.
Morrow, JD,
Hill KE,
Burk RF,
Nammour TM,
Badr KF,
and
Roberts LJD
A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism.
Proc Natl Acad Sci USA
87:
9383-9387,
1990
27.
Pratico, D,
Rossi E,
Merli M,
Riggio O,
FitzGerald GA,
and
Violi F.
Portal levels of the isoprostane F2-III, a marker of lipid peroxidation, do not correlate with increased portal pressure in cirrhotic patients.
J Investig Med
46:
430-434,
1998[ISI][Medline].
28.
Pratico, D,
Smyth EM,
Violi F,
and
FitzGerald GA.
Local amplification of platelet function by 8-Epi prostaglandin F2 is not mediated by thromboxane receptor isoforms.
J Biol Chem
271:
14916-14924,
1996
29.
Reilly, MP,
Pratico D,
Delanty N,
DiMinno G,
Tremoli E,
Rader D,
Kapoor S,
Rokach J,
Lawson J,
and
FitzGerald GA.
Increased formation of distinct F2 isoprostanes in hypercholesterolemia.
Circulation
98:
2822-2828,
1998
30.
Roberts, LJ II,
and
Morrow JD.
Isoprostanes. Novel markers of endogenous lipid peroxidation and potential mediators of oxidant injury.
Ann NY Acad Sci
744:
237-242,
1994[Abstract].
31.
Roberts, LJ II,
and
Reckelhoff JF.
Measurement of F(2)-isoprostanes unveils profound oxidative stress in aged rats.
Biochem Biophys Res Commun
287:
254-256,
2001[ISI][Medline].
32.
Rodriguez-Porcel, M,
Krier JD,
Lerman A,
Sheedy PF,
Romero JC, II,
Napoli C,
and
Lerman LO.
Combination of hypercholesterolemia and hypertension augments renal function abnormalities.
Hypertension
37:
774-780,
2001
33.
Rodriguez-Porcel, M,
Lerman A,
Best PJ,
Krier JD,
Napoli C,
and
Lerman LO.
Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity.
J Am Coll Cardiol
37:
608-615,
2001
34.
Schnackenberg, CG.
Physiological and pathophysiological roles of oxygen radicals in the renal microvasculature.
Am J Physiol Regulatory Integrative Comp Physiol
282:
R335-R342,
2002
35.
Schnackenberg, CG,
Welch WJ,
and
Wilcox CS.
TP receptor-mediated vasoconstriction in microperfused afferent arterioles: roles of O
36.
Stulak, JM,
Lerman A,
Caccitolo JA,
Wilson SH,
Romero JC,
Schaff HV,
Porcel MR,
and
Lerman LO.
Impaired renal vascular endothelial function in vitro in experimental hypercholesterolemia.
Atherosclerosis
154:
195-201,
2001[ISI][Medline].
37.
Stulak, JM,
Lerman A,
Rodriguez Porcel M,
Caccitolo JA,
Romero JC,
Schaff HV,
Napoli C,
and
Lerman LO.
Renal vascular function in experimental hypercholesterolemia is preserved by chronic antioxidant vitamin supplementation.
J Am Soc Nephrol
12:
1882-1891,
2001
38.
Takahashi, K,
Nammour TM,
Fukunaga M,
Ebert J,
Morrow JD,
Roberts LJ, II,
Hoover RL,
and
Badr KF.
Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2, in the rat. Evidence for interaction with thromboxane A2 receptors.
J Clin Invest
90:
136-141,
1992[ISI][Medline].
39.
Truog, WE,
Norberg M,
and
Thibeault DW.
Effects of 8-epi-prostaglandin F2 and U46,619 on pulmonary hemodynamics in piglets.
Biol Neonate
71:
306-316,
1997[ISI][Medline].
40.
Welch, WJ,
Peng B,
Takeuchi K,
Abe K,
and
Wilcox CS.
Salt loading enhances rat renal TxA2/PGH2 receptor expression and TGF response to U-46,619.
Am J Physiol Renal Physiol
273:
F976-F983,
1997
41.
Welch, WJ,
and
Wilcox CS.
Potentiation of tubuloglomerular feedback in the rat by thromboxane mimetic. Role of macula densa.
J Clin Invest
89:
1857-1865,
1992[ISI][Medline].
42.
Wilson, SH,
Best PJM,
Lerman LO,
Aviram M,
Richardson DM,
Holmes DR, Jr,
and
Lerman A.
Simvastatin preserves coronary endothelial function in hypercholesterolemia in the absence of lipid lowering.
Arterioscler Thromb Vasc Biol
21:
122-128,
2001
43.
Wilson, SH,
Best PJM,
Lerman LO,
Holmes DR, Jr,
Richardson DM,
and
Lerman A.
Enhanced coronary vasoconstriction to oxidative stress product, 8-epi-prostaglandin F2a, in experimental hypercholesterolemia.
Cardiovasc Res
44:
601-607,
1999
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