(Hypertension. 1996;27:631-635.)
© 1996 American Heart Association, Inc.
Articles |
Role of 20-HETE in Elevating Loop Chloride Reabsorption in Dahl SS/Jr Rats
From the Department of Physiology, Medical College of Wisconsin, Milwaukee.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Abstract In vivo tubular perfusion experiments were performed in normotensive Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats maintained from birth on a low salt (0.4% NaCl) diet to examine the role of 20-HETE in elevating loop Cl- transport in SS/Jr rats. Chloride reabsorption in the loop of Henle was significantly greater in SS/Jr than in SR/Jr rats (77±2% versus 57±3% of the perfused Cl- load). When the renal metabolism of arachidonic acid by P450 was blocked by the addition of 17-octadecynoic acid (10 µmol/L) to the perfusate, loop Cl- transport increased in SR/Jr rats to 70±2% of the delivered Cl- load, but it had no effect in SS/Jr rats. Conversely, addition of 20-HETE (10 µmol/L) to the perfusate lowered loop Cl- transport in S rats to 60±2% of perfused Cl- load, but it had no effect in SR/Jr rats. Addition of another endogenously formed HETE to the perfusate, 15-HETE (20 µmol/L), had no effect on Cl- reabsorption in the loop of Henle of SS/Jr rats. These findings indicate that endogenously produced P450 metabolites of arachidonic acid regulate Cl- transport in the loop of Henle of the rat in vivo and support the view that a diminished production of 20-HETE in the outer medulla of SS/Jr rats contributes to the elevation in loop Cl- transport and the resetting of the pressure-natriuresis relation in these animals.
Key Words: cytochrome P450 • cytochrome P450, inhibitors • hydroeicosatetraenoic acid • eicosanoids • kidney • loop of Henle • hypertension, renal
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Renal transplantation studies indicate that some form of renal dysfunction underlies the development of hypertension in human1 and genetic rat2 3 4 models; however, the factors responsible for altering kidney function in hypertension have not been identified. Previous studies indicated that the pressure-natriuresis relation is reset toward higher pressures before the development of hypertension in Dahl salt-sensitive (SS/Jr) rats5 6 7 and that this is associated with an elevation in Cl- reabsorption in the loop of Henle.7 8 9 More recently, we found that the production of a P450 metabolite of AA, 20-HETE, is reduced in the outer medulla of the kidney of SS/Jr rats.10 Since 20-HETE is an endogenously produced inhibitor of the Na+, K+, 2 Cl- transporter in rabbit thick ascending loop of Henle cells,11 12 13 a deficiency in the renal production of 20-HETE might contribute to the elevation in loop Cl- transport and the development of salt-sensitive hypertension in SS/Jr rats.10 This hypothesis is further supported by our recent observations that induction of the renal formation of 20-HETE with clofibrate prevents the development of hypertension in SS/Jr rats14 and that the P4504A2 genotype cosegregates with hypertension in an F2 population of rats derived from a cross of SS/Jr and Lewis rats.15 However, it remains to be established whether endogenously produced P450 metabolites of AA influence Cl- transport in the loop of Henle of the rat in vivo and whether this system contributes to the elevation in loop Cl- transport previously reported in SS/Jr rats.5 6 7 The purpose of the present study was to compare the effects of 20-HETE and blockade of the endogenous production of this compound with 17-ODYA on loop Cl- reabsorption in SS/Jr and SR/Jr rats using in vivo microperfusion of the loop of Henle.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Experiments were performed on 9-week-old, male, inbred SS/Jr and SR/Jr rats weighing between 200 and 250 g. The SR/Jr rats were purchased from Harlan Laboratories, Madison, Wis, and the SS/Jr rats were obtained from a breeding colony that we have maintained by brother-sister mating since 1991, which is before any evidence of genetic contamination of the commercial colony.16 Moreover, eight of the rats used in this study were genotyped by polymerase chain reaction for 40 markers scattered throughout the genome, and no evidence of genetic contamination was detected.
The rats were fed a low salt diet (0.4% NaCl by weight) from the time they were weaned at 3 weeks of age, and they were housed in an animal care facility at the Medical College of Wisconsin approved by the American Association for the Accreditation of Laboratory Animal Care. All protocols involving animals received careful review and prior approval by the Animal Care Committee of the Medical College of Wisconsin.
The rats were anesthetized with ketamine (30 mg/kg IM) and thiobutylbarbitol (30 mg/kg IP) and placed on a thermostatically controlled warming table to maintain body temperature at 37°C. Cannulas were placed in the right external jugular vein for intravenous infusions and in the right femoral artery for measurement of arterial pressure. An abdominal incision was made to expose the left kidney for micropuncture, and both ureters were cannulated for the collection of urine. After surgery, the rats were given an intravenous bolus of 1 to 2 mL 0.9% NaCl solution containing 6% albumin to replace surgical fluid losses and to return hematocrit to 45%. Thereafter, the rats received an intravenous infusion of 3% bovine serum albumin in a 0.9% NaCl solution at a rate of 20 µL · min-1 · 100 g body wt-1 throughout the experiment.
Loop Microperfusion Study
These experiments were performed on
17 SS/Jr and 16 SR/Jr rats
surgically prepared as described above. After surgery and a 60-minute
equilibration period, late proximal convoluted tubules along with their
associated early distal tubule were identified by injection of a small
bolus of a 5% solution of lissamine green into the tubule. Selected
tubules were then blocked with bone wax by use of a glass micropipette
and a hydraulic microdrive. A pipette connected to a nanoliter pump
(model A1400, World Precision Instruments) was inserted downstream of
the wax block to perfuse the loop of Henle with either a control or an
experimental perfusate at a rate of 20 nL/min. The control
perfusate contained (in mmol/L) NaCl 145, KCl 5,
MgSO4 1, CaCl2 1, and urea 5, 100 µCi/mL
[3H]inulin, and vehicle (0.02% ethanol). Experimental
perfusates contained a suicide-substrate
inhibitor of the renal metabolism of AA by
P450, 17-ODYA (10 µmol/L),17 18 20-HETE (10
µmol/L),
or another HETE formed in the outer medulla of the kidney, 15-HETE (20
µmol/L).10 After the tubule was perfused for 15 minutes
with either a control or an experimental perfusate, a
collection pipette was placed in the distal tubule and a timed tubular
fluid collection was obtained for measurement of sample volume, tubular
fluid inulin, and chloride concentrations. The concentration of 17-ODYA
used in these experiments was based on our previous findings that
17-ODYA blocks the formation of 20-HETE in renal microsomes and
microvessels at concentrations >1 µmol/L.17 18
In
perfused tubule studies, however, we found that a higher concentration
of 17-ODYA (10 µmol/L) had to be added to tubular fluid to block
tubuloglomerular feedback responses that are
dependent on the endogenous formation of
20-HETE.19 The reason for this is at present unknown,
but we suspect that it may be because 17-ODYA is highly lipid soluble
and a large portion of the infused compound is resorbed before it can
diffuse into and achieve an effective inhibitory
concentration (approximately 1 µmol/L) in thick ascending limb cells.
Similarly, 20-HETE is also extensively resorbed when added to tubular
fluid,19 and it also has to be added in a relatively high
concentration to tubular perfusates to raise intracellular
levels of 20-HETE and elicit functional responses in thick ascending
limb cells in vivo. In this regard, the concentration of 20-HETE used
in the present study was based on our previous finding that 10
µmol/L 20-HETE is required to restore
tubuloglomerular feedback responses when added
to the fluid perfusing the loop of Henle after inhibition of this
response with 17-ODYA.19
Clearance Studies
Additional studies were performed in 8
SS/Jr rats and 10 SR/Jr
rats to compare baseline renal function under the present
experimental conditions. These rats were surgically prepared as
described above except that [3H]inulin (1 µCi/mL) was
added to the intravenous infusion solution for measurement
of GFR, and an electromagnetic flow probe (2 mm) was placed around the
left renal artery for measurement of RBF. After surgery and a 1-hour
equilibration period, urine flow, hematocrit, RBF, GFR, mean
arterial pressure, and the urinary excretion of sodium,
potassium, and chloride were measured during two 30-minute clearance
periods.
Analytical Methods
The volume of the tubular fluid samples
was determined by
measurement of sample length in 1-µL capillary tubes. The
concentration of [3H]inulin in tubular fluid and plasma
samples was determined by use of a liquid scintillation
spectrophotometer. Tubular fluid chloride concentration was measured
with a microtitrator (model F-25, World Precision Instruments). The
percentage of the perfused load of chloride resorbed in the loop of
Henle was calculated as described previously.20
In the clearance studies, urine flow was determined gravimetrically. Sodium and potassium concentrations of urine and plasma samples were measured with a flame photometer, and chloride concentration was measured columetrically. GFR was calculated as the product of urine flow and the ratio of urine to plasma inulin concentration. Urinary excretion data, RBF, and GFR were all factored per gram of kidney weight.
Statistics
Data are presented as mean±SEM. The
significance of
differences within and between groups was evaluated by two-way
ANOVA factored for rat strain and treatment followed by a Duncan's
multiple range test as previously suggested by Raman et
al21 to deal with the potential problem of skewing of the
data due to an unequal number of tubules sampled per rat. A value of
P<.05 by two-tailed test was considered
significant.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Basal Renal Function
A comparison of baseline renal function in SS/Jr and SR/Jr rats is presented in the Table
. Mean arterial
blood pressures were not different in 9-week-old SS/Jr and SR/Jr
rats maintained on a low salt (0.4% NaCl) diet. RBF and GFR were about
25% lower in SS/Jr rats than in SR/Jr rats. Urine flow, sodium,
potassium, and chloride excretion were all significantly lower in SS/Jr
rats than in SR/Jr rats, and this was associated with lower fractional
excretions of Na+ and Cl- in the SS/Jr
rats compared with the values observed in SR/Jr rats.
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Loop Microperfusion Studies
The effects of inhibiting the
endogenous P450
metabolism of AA with 17-ODYA on loop
Cl- reabsorption are presented in Fig 1. Basal
reabsorption of water was similar in SS/Jr and
SR/Jr rats when the loop of Henle was perfused with a control solution
containing vehicle alone; however, loop Cl-
reabsorption was significantly greater in SS/Jr than in SR/Jr rats. The
percentage of the perfused Cl- load reabsorbed in
the loop of Henle averaged 77±2% in SS/Jr rats (n=27 nephrons in
17
rats) and only 57±3% of the perfused Cl- load in
SR/Jr rats (n=29 nephrons in 16 rats). Addition of 17-ODYA (10
µmol/L) to the perfusate had no effect on water reabsorption
in the loop of Henle in either group (Fig 1, top). Loop
Cl- reabsorption, however, increased to 70±2%
(n=19 nephrons in 9 rats) after 17-ODYA in SR/Jr rats, but it had no
significant effect on Cl- reabsorption in SS/Jr
rats (n=13 nephrons in 7 rats) (Fig 1, bottom).
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P<.05, a significant difference from the value obtained
during perfusion of vehicle in the same strain of rats.
The effects of 20-HETE on water and Cl-
reabsorption in SS/Jr and SR/Jr rats are presented in Fig 2.
Addition of 20-HETE to the fluid perfusing the loop of
Henle had no effect on water reabsorption in either group (Fig
2, top).
However, 20-HETE (10 µmol/L) significantly reduced the percentage of
the perfused load of Cl- reabsorbed in the loop of
Henle from 77±2% to 60±2% in SS/Jr rats, but it had no effect on
loop Cl- reabsorption in SR/Jr rats (Fig 2,
bottom). In 3 additional SS/Jr rats, the effects of adding another
endogenously formed HETE to the perfusate on loop
Cl- transport were examined in 8 nephrons. In these
experiments, the addition of 15-HETE (20 µmol/L) to the
perfusate had no effect on water or chloride reabsorption in
the loop of Henle. In tubules perfused with 15-HETE, the percentage of
water load reabsorbed in the loop of Henle averaged 62±2% and the
percentage of the perfused Cl- reabsorbed averaged
82±2% (n=8 nephrons in 3 rats). These values are not different
from
control values observed in tubules perfused with vehicle alone in SS/Jr
rats.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The present study examined the role of 20-HETE on the regulation of Cl- transport in the loop of Henle of SS/Jr and SR/Jr rats and the possible contribution of an abnormality in the renal production of this compound to the elevation of loop Cl- transport previously documented in SS/Jr rats.7 8 9 The loop microperfusion results again confirm previous reports that Cl- reabsorption in the loop of Henle is markedly elevated in SS/Jr rats compared with SR/Jr rats.7 8 9 The clearance data are also consistent with this view. Urine flow and sodium and chloride excretion were markedly reduced in 9-week-old normotensive SS/Jr rats maintained on a low salt diet compared with the corresponding values obtained in SR/Jr rats. The retention of water and electrolytes in SS/Jr rats was largely due to elevations in tubular reabsorption, because fractional excretions of sodium and chloride were 50% lower in SS/Jr than in SR/Jr rats. However, consistent with our previous findings in SS/Jr rats,6 RBF and GFR were significantly reduced in SS/Jr rats. Thus, changes in renal hemodynamics and the filtered load of sodium and chloride probably contribute to the inability of SS/Jr rats to excrete water and electrolytes as well as SR/Jr rats at equivalent levels of arterial pressure.
To examine the role of endogenous P450 metabolites of AA in
the regulation of loop Cl- transport, the loop of
Henle of SS/Jr and SR/Jr was perfused with a solution containing the
mechanism-based inhibitor P450 
-hydroxylase
inhibitor 17-ODYA at a concentration greater than that
previously reported to inhibit the formation of 20-HETE in renal
cortical microsomes17 and renal
microvessels.18 This same concentration has also been
reported to produce a gradual block of
tubuloglomerular feedback responses over a
15-minute period when added to solutions perfusing the loop of Henle of
the rat in vivo.19 Addition of 17-ODYA to the
perfusate increased Cl- reabsorption in the
loop of Henle of SR/Jr rats, whereas the addition of 20-HETE (10
µmol/L) to the perfusate inhibited Cl-
transport in the loop of Henle of SS/Jr rats. The effects of 20-HETE on
loop Cl- transport in SS/Jr rats appear to be
specific to this compound, since addition of an even higher
concentration of a closely related fatty acid produced in the outer
medulla of rats, 15-HETE, had no effect on loop Cl-
transport. Overall, these observations provide the first in vivo
evidence that endogenously formed P450 metabolites of AA,
in particular 20-HETE, participate in the regulation of loop
Cl- reabsorption. In this regard, the present
results are consistent with previous in vitro studies by
Escalante et al11 and Carroll et al12 in the
rabbit and Omata et al13 in the rat indicating that
20-HETE is the primary metabolite of AA produced by the thick ascending
limb and that this metabolite is a potent inhibitor of
Na+, K+, 2
Cl- transport in these cells.11
However, we have reported that 17-ODYA also inhibits the formation of
P450-derived metabolites of AA other than 20-HETE, such as 19-, 18-,
and 16-HETE and 11-, 12-, 14-, and 15-EETs and diHETEs.17
Thus, to the extent that other P450 metabolites of AA are produced in
the thick ascending loop of Henle, we cannot exclude the possibility
that inhibition of the endogenous formation of one or more
of these other compounds might also contribute to the elevation in loop
Cl- transport produced by 17-ODYA in Dahl SR/Jr
rats.
Another important aspect of the present study was to determine whether the previously reported abnormality in the production of 20-HETE in the outer medulla of the kidney of SS/Jr rats10 contributes to the elevation in loop Cl- transport seen in these rats.7 8 9 This was done by comparing the effects of a P450 inhibitor on loop Cl- transport in SS/Jr and SR/Jr rats. The present results indicating that addition of 17-ODYA to the perfusate markedly enhanced Cl- reabsorption in SR/Jr rats to the same level as that seen in SS/Jr rats but that it had no effect on Cl- transport in SS/Jr rats are consistent with this possibility. Further evidence that a deficiency in the endogenous production of 20-HETE may contribute to the elevated Cl- reabsorption in the loop of Henle of SS/Jr rats was obtained in the studies in which exogenous 20-HETE was added to the perfusate. In these studies, 20-HETE inhibited Cl- reabsorption in the loop of Henle of SS/Jr rats to the same level as that seen in SR/Jr rats, but it had no effect in SR/Jr rats, in which the production of 20-HETE in the outer medulla was higher than that seen in SS/Jr rats.10
The present results implicating a role for P450 metabolites of AA in altering loop chloride transport and sodium excretion in no way imply that this is the only mechanism that alters renal function in SS/Jr. Indeed, hypertension in SS/Jr is thought to be a polygenic disease, and there is considerable evidence that a number of different genetic loci that impact on renal function cosegregate with hypertension in this strain. In this regard, markers linked to renin,22 11ß-hydroxylase (a steroid hydroxylase),23 guanyl cyclase,24 inducible nitric oxide synthetase,25 the Sa gene26 (which maps to a region near the amiloride-sensitive sodium channel), and endothelin-2 synthase27 all cosegregate with arterial pressure in F2 crosses of SS/Jr and normotensive strains. Strain differences in the renal production of nitric oxide,28 prostaglandins,29 kallikrein,30 and EETs31 and abnormalities in the tubular effects of deoxycorticosterone and vasopressin32 have also been identified and suggested to play a role in altering renal function in Dahl salt-sensitive rats. However, it should be noted that except for inducible nitric oxide synthase, there is no genetic evidence linking any of these factors with the development of hypertension in SS/Jr, nor is there any evidence suggesting that these factors play a major role in the regulation of Cl- transport in the loop of Henle.
In the case of nitric oxide synthase, there is now some physiological evidence that this system contributes to the alterations in renal function in SS/Jr. In this regard, L-arginine has been reported to prevent the development of hypertension and renal disease in SS/Jr.28 The antihypertensive effects of L-arginine are associated with an elevation in renal interstitial hydrostatic pressure33 and a shift in the pressure-natriuresis relation toward lower pressures. However, L-arginine feeding does not alter Cl- transport in the loop of Henle of SS/Jr,34 indicating that this abnormality is not dependent on the nitric oxide system. Thus, although it is clear that there are strain differences in a number of renal paracrine systems that are important in the renal handling of sodium, the relative importance of each of these systems versus 20-HETE in altering renal function and in the development of hypertension in SS/Jr will have to be sorted out in future studies.
In summary, the present results indicate that 20-HETE is an endogenously formed inhibitor of Cl- transport in the loop of Henle of the rat in vivo and that the previously reported deficiency in the production of this substance in the outer medulla of the kidney of SS/Jr rats relative to other normotensive strains (SR/Jr and Lewis Wistar rats)10 15 contributes to the elevation in loop Cl- reabsorption in SS/Jr rats. The elevation in loop Cl- transport has previously been suggested to play an important role in the resetting of the pressure-natriuresis relation and the development of hypertensive SS/Jr rats.7 8 9 Moreover, our recent observations that P4504A genotype cosegregates with hypertension in an F2 population of rats derived from SS/Jr and Lewis Wistar rats and that induction of the production of 20-HETE15 in the kidneys of SS/Jr rats with clofibrate prevents the development of hypertension14 provide further support for this hypothesis.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This work was supported by grant HL-36279 from the National Institutes of Health.
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Footnotes |
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Reprint requests to Richard J. Roman, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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 M. Yu, B. Lopez, E. A. Dos Santos, J. R. Falck, and R. J. Roman Effects of 20-HETE on Na+ transport and Na+-K+-ATPase activity in the thick ascending loop of Henle Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2400 - R2405. [Abstract] [Full Text] [PDF]
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R. J. Roman, K. M. Hoagland, B. Lopez, A. E. Kwitek, M. R. Garrett, J. P. Rapp, J. Lazar, H. J. Jacob, and A. Sarkis Characterization of blood pressure and renal function in chromosome 5 congenic strains of Dahl S rats Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1463 - F1471. [Abstract] [Full Text] [PDF]
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J. M. Williams, X. Zhao, M. H. Wang, J. D. Imig, and D. M. Pollock Peroxisome Proliferator-Activated Receptor-{alpha} Activation Reduces Salt-Dependent Hypertension During Chronic Endothelin B Receptor Blockade Hypertension, August 1, 2005; 46(2): 366 - 371. [Abstract] [Full Text] [PDF]
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E. A. Dos Santos, A. J. Dahly-Vernon, K. M. Hoagland, and R. J. Roman Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R58 - R68. [Abstract] [Full Text] [PDF]
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 H. Wang, Y. Zhao, J. A. Bradbury, J. P. Graves, J. Foley, J. A. Blaisdell, J. A. Goldstein, and D. C. Zeldin Cloning, Expression, and Characterization of Three New Mouse Cytochrome P450 Enzymes and Partial Characterization of Their Fatty Acid Oxidation Activities Mol. Pharmacol., May 1, 2004; 65(5): 1148 - 1158. [Abstract] [Full Text]
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K. M. Hoagland, A. K. Flasch, A. J. Dahly-Vernon, E. A. dos Santos, M. A. Knepper, and R. J. Roman Elevated BSC-1 and ROMK Expression in Dahl Salt-Sensitive Rat Kidneys Hypertension, April 1, 2004; 43(4): 860 - 865. [Abstract] [Full Text] [PDF]
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C. L. Laffer, M. Laniado-Schwartzman, A. Nasjletti, and F. Elijovich 20-HETE and Circulating Insulin in Essential Hypertension With Obesity Hypertension, February 1, 2004; 43(2): 388 - 392. [Abstract] [Full Text] [PDF]
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K. M. Hoagland, A. K. Flasch, and R. J. Roman Inhibitors of 20-HETE Formation Promote Salt-Sensitive Hypertension in Rats Hypertension, October 1, 2003; 42(4): 669 - 673. [Abstract] [Full Text] [PDF]
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K. M. Hoagland, K. G. Maier, and R. J. Roman Contributions of 20-HETE to the Antihypertensive Effects of Tempol in Dahl Salt-Sensitive Rats Hypertension, March 1, 2003; 41(3): 697 - 702. [Abstract] [Full Text] [PDF]
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C. L. Laffer, M. Laniado-Schwartzman, M.-H. Wang, A. Nasjletti, and F. Elijovich 20-HETE and Furosemide-Induced Natriuresis in Salt-Sensitive Essential Hypertension Hypertension, March 1, 2003; 41(3): 703 - 708. [Abstract] [Full Text] [PDF]
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 C. L. Laffer, M. Laniado-Schwartzman, M.-H. Wang, A. Nasjletti, and F. Elijovich Differential Regulation of Natriuresis by 20-Hydroxyeicosatetraenoic Acid in Human Salt-Sensitive Versus Salt-Resistant Hypertension Circulation, February 4, 2003; 107(4): 574 - 578. [Abstract] [Full Text] [PDF]
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A. J. Dahly, K. M. Hoagland, A. K. Flasch, S. Jha, S. R. Ledbetter, and R. J. Roman Antihypertensive effects of chronic anti-TGF-beta antibody therapy in Dahl S rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R757 - R767. [Abstract] [Full Text] [PDF]
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M. Szentivanyi Jr., A.-P. Zou, D. L. Mattson, P. Soares, C. Moreno, R. J. Roman, and A. W. Cowley Jr. Renal medullary nitric oxide deficit of Dahl S rats enhances hypertensive actions of angiotensin II Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R266 - R272. [Abstract] [Full Text] [PDF]
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P. A. Ortiz and J. L. Garvin Role of nitric oxide in the regulation of nephron transport Am J Physiol Renal Physiol, May 1, 2002; 282(5): F777 - F784. [Abstract] [Full Text] [PDF]
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M.-H. Wang, B. A. Zand, A. Nasjletti, and M. Laniado-Schwartzman Renal 20-hydroxyeicosatetraenoic acid synthesis during pregnancy Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R383 - R389. [Abstract] [Full Text] [PDF]
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 R. J. Roman P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiol Rev, January 1, 2002; 82(1): 131 - 185. [Abstract] [Full Text] [PDF]
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R. Quigley, M. Baum, K. M. Reddy, J. C. Griener, and J. R. Falck Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport Am J Physiol Renal Physiol, June 1, 2000; 278(6): F949 - F953. [Abstract] [Full Text] [PDF]
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J. M. Lasker, W. B. Chen, I. Wolf, B. P. Bloswick, P. D. Wilson, and P. K. Powell Formation of 20-Hydroxyeicosatetraenoic Acid, a Vasoactive and Natriuretic Eicosanoid, in Human Kidney. ROLE OF CYP4F2 AND CYP4A11 J. Biol. Chem., February 11, 2000; 275(6): 4118 - 4126. [Abstract] [Full Text] [PDF]
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 J. H. Capdevila, J. R. Falck, and R. C. Harris Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase J. Lipid Res., February 1, 2000; 41(2): 163 - 181. [Abstract] [Full Text]
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D. W. Good, T. George, and D. H. Wang Angiotensin II inhibits HCO-3 absorption via a cytochrome P-450-dependent pathway in MTAL Am J Physiol Renal Physiol, May 1, 1999; 276(5): F726 - F736. [Abstract] [Full Text] [PDF]
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O. Ito and R. J. Roman Role of 20-HETE in Elevating Chloride Transport in the Thick Ascending Limb of Dahl SS/Jr Rats Hypertension, January 1, 1999; 33(1): 419 - 423. [Abstract] [Full Text] [PDF]
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P. Su, K. M. Kaushal, and D. L. Kroetz Inhibition of renal arachidonic acid omega -hydroxylase activity with ABT reduces blood pressure in the SHR Am J Physiol Regulatory Integrative Comp Physiol, August 1, 1998; 275(2): R426 - R438. [Abstract] [Full Text] [PDF]
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 M.-H. Wang, E. Brand-Schieber, B. A. Zand, X. Nguyen, J. R. Falck, N. Balu, and M. L. Schwartzman Cytochrome P450-Derived Arachidonic Acid Metabolism in the Rat Kidney: Characterization of Selective Inhibitors J. Pharmacol. Exp. Ther., March 1, 1998; 284(3): 966 - 973. [Abstract] [Full Text]
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O. Ito, M. Alonso-Galicia, K. A. Hopp, and R. J. Roman Localization of cytochrome P-450 4A isoforms along the rat nephron Am J Physiol Renal Physiol, February 1, 1998; 274(2): F395 - F404. [Abstract] [Full Text] [PDF]
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T. W. Wilson, M. Alonso-Galicia, and R. J. Roman Effects of Lipid-Lowering Agents in the Dahl Salt-Sensitive Rat Hypertension, January 1, 1998; 31(1): 225 - 231. [Abstract] [Full Text] [PDF]
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J. Jiang, D. E. Stec, H. Drummond, J. S. Simon, G. Koike, H. J. Jacob, and R. J. Roman Transfer of a Salt-Resistant Renin Allele Raises Blood Pressure in Dahl Salt-Sensitive Rats Hypertension, February 1, 1997; 29(2): 619 - 627. [Abstract] [Full Text]
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D. E. Stec, D. L. Mattson, and R. J. Roman Inhibition of Renal Outer Medullary 20-HETE Production Produces Hypertension in Lewis Rats Hypertension, January 1, 1997; 29(1): 315 - 319. [Abstract] [Full Text] [PDF]
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