Journal of the American Society of Nephrology 1567

Segmental Chloride Transport in the Dahl-S Rat KidneyDuring L-Arginine Administration1Kent A. Kirchner,2 Bridget A. Crosby, Ami P. Patel, and Joey P. Granger

K.A. Kirchner. BA. Crosby, AR. Patel, J.P. Granger.

Department of Medicine and Physiology, Universily ofMississippi Medical Center, Jackson, MS

(J. Am. Soc. Nephrol. 1995; 5:1567-1572)

ABSTRACTi-Arginine normalizes pressure natriuresis in DahI salt-sensitive (DS) rats. The nephron segments responsible

for improvement in sodium chloride handling duringi-arginine administration are unknown. Micropunc-

ture techniques were used to examine fluid and chlo-ride transport along superficial nephron segments inDS rats maintained on an 8% sodium diet and givenL-arginine or vehicle ip for 3 wk. Renal perfusion

pressure in vehicle-treated DS rats was reduced to thatof i-arginine-treated DS rats with an aortic snare. DahI

salt-resistant (DR) rats receiving vehicle were exam-med for comparison. In agreement with previous

studies, urinary sodium chloride excretion was

greater (P < 0.05) In L-arginine DS rats than in vehicleDS rats and not different from DR rats at equivalentrenal perfusion pressures. Whole-kidney and single-nephron GFR were not different (P = not significant)among groups. Fractional proximal tubule chlorideand fluid reabsorption was not different amonggroups. Fractional loop chloride reabsorption wasgreater in vehicle-treated DS rats than in DR rats (58.5± 1 .5 versus 46.6 ± 1.7%; P < 0.05), confirming the

enhanced chloride reabsorption at this location in DSrats previously reported. Fractional loop chloride re-absorption was identical in vehicle- and L-arginine-

treated DS rats (58.4 ± 1 .4 versus 58.9 ± 3.9%; P = not

significant). Fractional loop fluid reabsorption was not

different among groups. Fractional distal fluid andchloride reabsorption was not different between DSrat groups. These data suggest that the improvedpressure-natriuresis relationship produced by 1-argi-nine administration to DS rats is not due to the en-hanced delivery from superficial nephrons, but possi-bly results from ( 1) the inhibition of reabsorption injuxtamedullary nephrons or (2) an effect on transportin the collecting system.

� Received November 5, �993. Accepted September 6, 1994.2corespondence to Dr. K.A. Kirchner, University of Mississippi Medical center.

2500 North State Street, Jackson, MS 39216.4505.

1046.6673/0508-1 567$03.00/0Journal of the American Society of NephrologyCopyright © 1995 by the American Society of Nephrology

--� Key Words: Pressure natriuresis, hypertension. nitric oxide.

endothelial derived relaxing factor

T he administration of the amino acid L-arginine

prevents the development of hypertension in

Dahb salt-sensitive (DS) rats ( 1 .2). We have previously

� �- � - shown that this effect Is associated with improvement

in the blunted relationship between renal perfusion

pressure and urinary sodium excretion that usually

characterizes sodium handling in these animals (2).

Neither the mechanism nor the tubule segment(s)

responsible for the Improvement in sodium handling

induced by L-arglfllne has been identified. In previous

studies, we, as well as Roman and Kaldunski, have

reported that DS rats have greater chloride reabsorp-

tion in cortical loop segments than do Dahl salt-

resistant (DR) rats when both are examined at equiv-

alent renal perfusion pressures (3,4). This abnor-

mality is present before the development of hyperten-

sion (4,5). Because L-arginine has no effect on renal

sodium excretion in DR rats. it seemed reasonable to

postulate that L-arglnine’s primary effect may be to

correct the abnormality In cortical loop sodium chlo-

ride transport in DS rats. On the other hand, because

pressure natriuresis is felt to be related to events

occurring in juxtamedullary nephrons or the collect-

ing duct (6-9), L-arglnlne could alter transport at sites

beyond the distal convoluted tubule or in deep

nephrons. This study was designed to examine fluid

and chloride handling in the superficial cortical

nephron segments of L-arglnine or vehicle DS rats

maintained on an 8% sodium diet to examine the

location for L-arginine’s effect on sodium excretion.

METHODS

Male DS and DR Rapp rats (Harlan Sprague-Dawley. mdi-

anapolis. IN) were maintained on tap water and standardrodent chow (20 �tM Na/g ofchow) for 72 h after arrival in ourfacility. All animals were housed according to institutional

guidelines. and the studies were approved by the Animal

Care and Use Committee of the University of Mississippi

Medical Center. All rats were then placed on 8% sodium chow

and given tap water to drink ad libitum. DS rats were given ipinjections of either the hydrochloride salt of L-arginine (Sig-

ma Chemical Co. , St. Louis, MO) or its vehicle for 3 wk. DR

rats received only the vehicle for L-arginine. because we have

previously shown that L-arginine has no effect on bloodpressure or sodium chloride handling in these animals (2).After 3 wk on the diet. rats were anesthetized with an ipinjection of5 sec-butyl-5 ethyl-2-thiobarbituric acid (Inactin:Promonto, Hamburg. Germany) in a dose of 80 mg/ kg.Animals were placed on a thermostatically controlled animaltable, and body temperatures were maintained at 37#{176}Cwitha servo activated controller (Vestavia Scientific Co. , VestaviaHills, AL). After tracheostomy. PE-50 (Clay Adams, Parsip-

pany, NJ) polyethylene catheters were placed in the femoral

L-Arginine and Nephron Chloride Uptake

1568 Volume 5� Number 8 . 1995

artery for the continuous measurement of mean arterialpressure and in the jugular vein for lv infusions. A flangedPE-50 polyethylene catheter was placed in the bladder forurine collection. From the start of surgery. isotonic Ringer’ssolution containing 5% polyfructosan (Inutest; LaevasanGeselbschaft, Llnz, Austria) was infused at a rate of 1 .5 mL/h.The abdomen was opened through a midline incision. and anultramicroclamp was placed above the renal arteries for themanipulation of renal perfusion pressure. The left kidney

was exposed through a subcostal incision and gently sepa-

rated from the adrenal gland and perirenal fat. The kidneywas placed in a plastic cup, and the upper ureteral segmentwas cannubated with PE-50 polyethylene tubing. Agar wasplaced around the kidney to form a well. The kidney was thenbathed with mineral oil warmed to 37#{176}C.To compensate forthe reduction in plasma volume attendant on abdominalsurgery, rats received a 1 .2 mL/ 100 g body wt infusion of 5%

albumin Ringer’s solution during the surgical procedure.Additionally. all rats received an Infusion of 154 mM sodiumchloride containing 1 % bovine serum albumin at a rate of

100 pL/min throughout the study. After the surgical proce-dure, cortical surface convolutions of three to four latestproximal and three to four earliest distal tubules were iden-tified by observing the passage of three to four O.05-m.Lboluses of 7.5% FD&C (Keystone Aniline and Chemical Co.,Chicago, IL) green dye. In DS rat groups, one to two latestdistal tubule segments were also identified.

After a 60-mm surgical recovery period, tubule fluid sam-ples were obtained in random order from the previously

identified proximal, early distal, and in DS rats, late distalsites over a 90-min experimental period. The method oftubule fluid sampling has been described by us previously(3.5). TImed collections of tubule fluid were obtained for thedetermination of flow rate and inulin and chloride concen-trations. Urine was collected under oil in preweighed vials forthe duration of the experimental period. Blood was obtainedat the beginning and end of the experimental period for themeasurement of inulin, sodium, and chloride concentra-tions.

Three groups of rats were examined. All rats were ofcomparable age at the time of study. The first group (N = 7)

was DR rats treated with the vehicle for L-arginine adminis-tration. The second group ofrats (N = 7) was DS rats that had

received the vehicle for L-arglnlne administration. In theseanimals, renal perfusion pressure was reduced to the level ofthe L-arginine-treated DS rats before the surgical recoveryperiod by tightening the aortic clamp. The third group of rats(N = 8) was DS rats that received daily ip injections of

L-arglnine in a dose of 300 mg/kg body wt. The last dose ofL-arglnine was administered approximately 18 h before theacute study. At the end of the experimental period, animalsfrom all groups were euthanized by exsanguination while stillunder anesthesia, and the kidneys were removed andweighed.

Analytical Techniques

Urinary flow rate was determined by change in weight of

preweighed vials. Chloride concentrations in serum andurine were analyzed amperometrically. Inulin concentrationIn urine and plasma was determined by the diphenylaminemethod of Walser et a!. (10). Tubule fluid volume was mea-sured in constant-bore glass tubing with a microslide com-parator (Gaertner Scientific, Chicago, IL). Tubule fluid inulinconcentration was determined by the method of Vurek andPegram (11). Tubule fluid chloride concentration was deter-

mined by electrometric titration according to the secondmethod of Ramsey et a!. (12).

Analysis of DataBecause of the genetic contamination of Dahl-Rapp rats in

early 1993. only data from rats obtained before February

1993 were used for analysis. The determination of the con-centratlons of inulin, sodium, and chloride in blood andurine and urinary flow rate permitted the calculation of

whole-kidney GFR and urinary excretion rates ofsodium andchloride according to standard expressions. The measure-ment of flow rate and inulin and chloride concentrations in

tubule fluid samples allowed the determination of single-nephron GFR (SNGFR) and fractional delivery rates of chbo-ride and fluid to puncture sites as previously described (3).The fraction of ifitered chloride reabsorbed between twonephron segments, A and B, was calculated according to thefollowing expression:

l(TF/PY�cI/IN - (TF/P)BcI/INI X 100

where (TF/P)cl,IN is the tubule fluid to plasma chloride andinulin ratio. This calculation was performed for each individ-ual animal from the mean values obtained In that individual

animal. Absolute chloride reabsorption was then calculatedin each individual animal from the mean values for earlydistal SNGFR nephron ifitered load, and appropriate valuefor fractional reabsorption were determined in that animal.In all statistical treatments, N represents the number of

animals and not tubules. Analysis of variance was used todetermine statistical significance between groups. If analysisof variance indicated that a statistical significance existed,then a Student-Newman-Keuls test was used to determinestatistical significance among the three groups ( 13). Statls-tical significance was set at the P < 0.05 level.

RESULTS

The whole-kidney and blood values in each of the

three study groups are summarized in Table 1 andFigure 1 . Mean arterial pressure was less (P < 0.05) in

L-arginine-treated DS rats than in vehicle-treated DSrats and not different (P = not significant ENS]) from

mean arterial pressure in DR rats. Renal perfusion

pressure was not different (P = NS) among any of the

three groups. mum clearance determined at approx-

imately equivalent renal perfusion pressures (Table 1)tended to be slightly less in vehicle-treated DS rats

than in other groups, but this did not reach statisticalsignificance. Absolute and fractional urinary sodium

excretion rates were greater (P < 0.05) in L-arginine-

treated DS rats than In vehicle-treated DS rats. So-dium excretion was not different (P = NS) betweenL-arginine-treated DS rats and DR rats. Urinary chbo-

ride excretion demonstrated a similar pattern (Figure1 ). There were no differences in plasma sodium or

chloride concentrations among the three groups.

SNGFR determined from either proximal or distal

puncture sites was not different (P = NS) among any of

the three experimental groups (Figure 2).

Absolute and fractional chloride delivery rates to the

latest accessible segment of the proximal convoluted

tubule were not different between any of the three rat

groups (Table 2). Fractional proximal chloride reab-

I:� .�:,o� 4

C.)a 2

IL.

usa s L-ARG

80

70

�E 60

.2.E. 50

� 40

� 30

� 20cLa.

‘CI) 10

Kirchner et al

Journal of the American Society of Nephrology 1569

TABLE 1 . Mean arterial pressure, inulin clearance, and electrolyte excretion rates in DahI rats maintained on8% sodium intake and given i-arginine or its vehicle for 3 wk#{176}

RatMAP

(mm Hg)RPP

(mm Hg)

Cm (4/mmper g

kidney wt)

UNOV (nmol/minper g kidney WI)

FeNa (%)UCJV (nmol/minper g kidney WI)

PNa(mmol/L)

PCI(mmol/L)

DR (N = 7)DSVehicle

(N = 7)

DSL-ArginineN = 8)

130 ± 1b

167± 7

129�3b

130 ± 1124±3

127 ±3

1,144 ± 171861 ±45

1,121 ± 178

9,211 ± 1,305b

2,793 ±428

9,370�904b

5.27 ± 0.67b2.07 ±0.28

6.14± 102b

9,338 ± 1,313b

3,128±462

8897#{247}476b

159 ± 3157 ±3

157 ±2

122 ±2118±2

118 ±2

a Values are mean ± SE; N. number of rats studied; MAP. mean arterial pressure; RPP. renal perfusion pressure; On, inulin clearance; UNaV. absoluteurinary sodium excretion; FeNa. fractional urinary sodium excretion; uciv. absolute urinary chloride excretion. PNa. plasma sodium concentration;PCI. plasma chloride concentration. cln and electrolyte excretion rates were determined at renal perfusion pressures listed in the second column.b p < 0.05 versus DS vehicle.

QR

us10 us L-ARG

0

Figure 1 . Fractional urinary chloride excretion in DR rats (R),DS rats (S), and DS rats treated with i-argmnmne (L-ARG) dailyfor 3 wk. Rats were studied at equivalent renal perfusionpressures. � P < 0.05 versus DS rats.

Proximal Tubule Distal Tubule

Figure 2. SNGFR in DR rats, DS rots, and DS rats treated withi-argmnine. See legend to Figure 1 for an explanation ofabbreviations.

sorption (Figure 3) and fractional proximal fluid reab-

sorption (Figure 4) were also not different among anyof the three rat groups.

Absolute and fractional chloride delivery rates to the

early distal tubule puncture site were significantly

less (P < 0.05) in vehicle-treated DS rats than In DR

rats (Table 2). Absolute and fractional chloride deliv-

ery rates to early distal tubule puncture sites were not

different (P = NS) between DS rats that had received

L-arglnine and DS rats that has received vehicle.

Fractional loop segment chloride reabsorption was

greater (P < 0.05) in both DS rat groups than in DR

rats (Figure 3). Fractional loop segment chloride reab-sorption was almost identical in vehicle-treated and

L-arginine-treated DS rats (58.4 ± 1 .4 versus 58.9 ±

3.9%; P = NS). Fractional loop segment fluid reabsorp-

tion tended to be greater In both DS rat groups

compared with DR rats, but this difference did notreach statistical significance (Figure 4). Fractional

fluid reabsorption in the loop segment was not differ-

ent between vehicle-treated and L-arginine-treated DS

rats.

There were no differences In absolute or fractional

chloride delivery to the late distal tubule puncture site

between vehicle-treated and L-arginlne-treated DS

rats (Table 3). Fractional chloride reabsorption in the

distal tubule was almost identical between these two

DS rat groups (DS. 5.0 ± 1 .6% versus DS L-arginine,

5.4 ± 3.4%; P = NS) (Figure 3). Fractional fluid

reabsorption in the distal tubule was likewise notdifferent between vehicle-treated and L-arginlne-

treated DS rats (Figure 4).

DISCUSSION

In previous work, we have shown that either theacute or the chronic administration of L-arglnlne to DS

rats restores the abnormal pressure-natriuresis reba-

tionship that usually characterizes these animals (2).

This response, however, was not observed with equiv-

alent amounts of o-arginine and could be prevented

by the concomitant administration of the nitric oxide

synthase inhibitor N#{176}-nltro-L-arginine-methylester

(L-NAME). L-arginine, however, had no effects on pres-sure natriuresis in DR rats. This study confirms the

central findings of our previous work, that at equivalent perfusion pressures, urinary sodium chloride

excretion is greater in DS rats receiving L-argifllne

than in DS rats receiving L-arginine vehicle and not

different from DR rats. This study also extends these

findings by examining fluid and chloride handling In

cortical nephron segments in these groups. The re-

suits show that SNGFR in cortical nephrons and.

usu s

Proximal Tubule Loop of Henle Distal Tubule

Figure 3. Fractional chloride reabsorption along the nephronexpressed as percent filtered chloride load in DR rats, invehicle-treated DS rats, and in i-argmnine-treated DS rats. �< .05 versus DR rats. See legend to Figure 1 for an explana-tion of abbreviations.

�- 80

I� 600

8 50150cc 40

30

20

10

0 Proximal Tubule Loop of Henle Distal Tubule

Figure 4. Fractional fluid reabsorption along the nephronexpressed as percent filtered fluid load in DR rats, in vehicle-treated DS rats, and in L-arglnlne-treated DS rats. See legendto Figure 1 for an explanation of abbreviations.

thus, filtered loads of sodium and chloride were not

different between vehicle-treated and L-arginlne-

treated DS rats. There were also no differences in

chloride and fluid reabsorption in the proximal tu-

bube, loop segment, or distal convoluted tubule be-

tween DS rats receiving L-arginlne and DS rats receiv-

Ing L-arginlne vehicle. Thus, these data suggest that

the effect of L-arginine to increase urinary sodium

excretion and restore the relationship between renal

perfusion pressure and sodium excretion in the DS rat

results from an effect on sodium chloride transport

beyond the distal convoluted tubule, perhaps in the

collecting duct. Alternatively L-arginine could increase

delivery out ofjuxtamedullary nephrons.

The mechanism by which L-arginine increases so-

dium chloride excretion in DS rats remains to be

determined. We have previously shown that L-arginine

improves the autoregubation of GFR in the DS rat (2).

In those studies, as in this investigation, whole-kidney

GFR was slightly greater in L-arginine-treated DS rats

compared with vehicle-treated DS rats at each indi-

vidual renal perfusion pressure examined. Although

these differences did not reach statistical significance,

increases in these parameters are likely to be impor-

tant contributors to the overall improvement in renal

sodium chloride excretion observed in L-arginine-

treated rats. On the other hand, we, as well as Romanand Kaldunski, have shown that the cortical loop

segment of DS rats has enhanced chloride reabsorp-

tion relative to that of DR rats (3,4). Furthermore, this

finding Is present before exposure to a high-salt diet

and before the development of hypertension (4,5). Wehave proposed that this abnormality may be Impor-tant for the blunted natriuretic capacity and the at-

tenuated pressure-natriuresis relationship found inDS animals. This study confirms that loop chloridereabsorption is greater in hypertensive DS rats than inDR rats when both are examined at equivalent renal

perfusion pressures . Interestingly and unexpectedly,

the chronic administration of L-arginine to DS rats

had no effect on loop chloride reabsorption, even

though It prevented the development of hypertensionand increased urinary sodium chloride excretion torates not different from those observed in DR rats. In

fact, loop chloride reabsorption was almost Identical

In DS rats receiving L-arglnine or its vehicle and in

both circumstances was greater than that observed in

DR rats (Figure 3). Thus, a reduction in loop chloride

uptake is not a requirement for either the prevention

of hypertension or the improvement in sodium chlo-ride excretion that follows L-arginine administration to

the DS rat.

L-Arginine and Nephron Chloride Uptake

1570 Volume 5 . Number 8 . ]995

TABLE 2. Absolute and fractional chloride delivery to puncture sites in DahI rats maintained on 8% sodiumintake and given L-arginine or its vehiclea

Late Proximal Early Distal Late Distal

Rat FDCI(%)

ADCI(pmol/min)

TFCI(mmoi/L)

FDCI(%)

ADCI(pmoi/min)

TFCI(mmol/L)

FDCI(%)

ADCI(pmol/mmn)

TFCI(mmol/L)

DR (N = 7) 65.1 ± 2.8 2,963 ± 583 153 ± 4 18.5 ± 2.3 838 ± 177 59 ± 4 ND ND NDDS Vehicle 68.3 ± 1 .6 2, 1 19 ± 174 152 ±4 10.4 ± 0.7b 312 ± 20b 43 ±2 5.4 ± 2 166 ± 38 43 ± 6

(N = 7)

DS i-Arginine 73.4 ± 3.7 3,051 ± 506 158 ± 5 14.3 ± 1.8 568 ± 89 52 ± 5 8.3 ± 1.4 281 ± 34 56 ± 4(N = 8)

a Values are mean ± SE; FDCI, fractional delivery of chloride; ADCI. absolute delivery of chloride; TFCI. tubule fluid to plasma chloride ratio; ND. notdone.b p < .05 versus DR.

80

70

60

0V

0�V� 50

�e 40

� 30Ce

� 20C.)(5

(� 10

V

U-

(5C0

C.)

15

IL

0

usu s

Kirchner et al

Journal of the American Society of Nephrology 1571

Chen and associates have recently shown that di-

etary L-arginine administration prevents the hyper-

tensive nephrosclerosls that occurs in DS rats main-

tained on a high-sodium diet ( 1 4). On the basis of their

findings, the greater urinary sodium chloride excre-

tion observed in DS rats chronically treated with

L-arginine in our study could have resulted from the

prevention of structural renal damage. On the other

hand, we have previously shown that the acute iv

administration of L-arginine improves blood pressure

and normalizes sodium excretion even in hypertensive

DS rats (5). Thus, the improvement in sodium chloride

excretion after chronic L-arglnlne administration in

this study may have resulted from a combination of

the prevention of structural damage and specific ef-

fects on electrolyte transport.The finding that L-arginine improves the relation-

ship between pressure and sodium excretion withoutaltering chloride. and presumably sodium, reabsorp-

tion in the cortical proximal tubule, loop, or distalconvoluted tubule would be consistent with our cur-

rent understanding of the mechanisms and tubule

segments responsible for the pressure-natriuresis re-

latlonship. Kunau and Lameire demonstrated that, innormotensive rats, acute increases in renal perfusion

pressure increase urinary sodium excretion without

altering tubular sodium reabsorption up to the super-

ficial late distal tubule (7). In subsequent studies,

Haas and associates, as well as Roman, have shown

little or no effect of changes in renal perfusion pres-sure on delivery out of cortical proximal tubule seg-

ments (8,9). Roman and Zou have recently proposed

that changes in renal perfusion pressure influencetubular reabsorption through changes in medullary

hemodynamics and renal interstitial hydrostatic pres-

sure ( 15). Furthermore, the direct administration of

L-arginine analogs that inhibit nitric oxide synthase

reduces renal interstitial pressure and urinary so-

dium excretion when infused directly into the renal

medulla ( 16). This occurs without altering blood pres-

sure or GFR. The relationship between renal perfusion

pressure and renal interstitial hydrostatic pressure

has been found to be abnormal In hypertensive DSrats and Is improved by L-arginine administration( 1 7). Husted and Stokes have shown that cells from

the inner medullary collecting duct of kidneys from

prehypertensive DS rats transport more sodium than

do cells obtained from a similar location in DR rats

( 18). L-Arginine analogs have been reported to alter

transport-dependent oxygen consumption in suspen-

slons of Inner medullary collecting duct cells in vitro( 19). Thus, L-arginine could improve sodium excretion

and perhaps pressure natriuresis by altering sodium

reabsorption and sodium transport in the renal me-

dulla. Additional studies will be necessary to deter-

mine which sites account for the Improvement inpressure natriuresis observed during L-arglnlne ad-

ministration.Finally. most investigators attribute the effects of

L-arginine on blood pressure and renal function to Its

ability to enhance nitric oxide production ( 1 ,2,20).

Whether the improvement In blood pressure and so-

dium excretion found In DS rats Is related to changes

in nitric oxide production or release was not examined

in this study. Westberg and associates have reported

that urinary NO2 ± NO3 excretion, a putative Index of

nitric oxide activity, Is bower in DS rats than in DR rats

after exposure to a high-salt diet and Is Increased by

L-arginine administration (2 1 ). We have previously

shown that the improvements in these parameterscan be prevented by the administration of NG�nltro�L�

arginine methylester (2). Furthermore, the improve-ment in blood pressure during L-arginlne administra-

tion to DS rats Is associated with significant Increases

in urinary cGMP excretion, the final messenger for theinhibition of sodium reabsorption in terminal nephron

segments ( 1). Nitric oxide has also been shown to play

an important role in the regulation of pressure natri-

uresis in normal animals (2 1-24). Thus, It seems

reasonable to suggest that the Improvement In so-

dium excretion in DS rats after L-arglnine administra-

tion in this study was also mediated through the nitric

oxide pathway.

In summary, this study confirms our previous workthat L-arginlne given to DS rats maintained on a

high-salt diet prevents the development of hyperten-

sion and improves their ability to excrete sodium

chloride. The improvement in sodium chloride excre-

tion is not the result of enhanced delivery from cortical

tubule segments nephrons but may result from the

inhibition of transport In the collecting system. Alter-

natively. L-arglnine could Increase delivery from ju.x-

tamedublary nephrons.

ACKNOWLEDGMENTSThe authors thank Barbara Anderson and Jackie Jordan for their

excellent secretarial assistance. This study was supported by GrantsHL-1 1678. HL-33049. and HL-51971 from the NIH and American

Heart Association Grant 92-6-45. Dr. Granger is an EstablishedInvestigator for the American Heart Association (892631.

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2. Patel A, Layne DS, Watts D, Kirchner KA: L-arginineadministration normalizes pressure-natriuresis in hy-pertensive Dahl rats. Hypertension l993;22:863-869.

3. Kirchner KA: Greater loop chloride uptake contributesto blunted pressure natriuresis in Dahl salt-sensitiverats. J Am Soc Nephrol 1990; 1:180-186.

4. Roman DRJ, Kaldunski ML: Enhanced chloride reab-sorption in the 1oop of Henle in Dahi salt-sensitive rats.Hypertension 1991 ; 17: 10 18-1024.

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8. Haas JA, Granger JP, Knox FG: Effect of renal perfusionpressure on sodium reabsorption from proximal tubules

L-Arginine and Nephron Chloride Uptake

1572 Volume 5� Number 8 . 1995

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