feed-back response which, although absent in free-flowing nephrons, can still be elicited by loop of

23 Pages·2005·2.76 MB·English

Journal ofPhysiology (1988), 402, pp. 473-495 473
With 5 text-figures
Printed inGreat Britain
THE CONTROL OF GLOMERULAR FILTRATION RATE AND RENAL
BLOOD FLOW IN CHRONICALLY VOLUME-EXPANDED RATS
BY J. M. DAVIS, D. A. HABERLE AND T. KAWATA*
From the Department ofPhysiology, University ofMunich, Pettenkoferstr. 12,
D-8000 Munich 2, F.R.G.
(Received 13 November 1987)
SUMMARY
1. Chronic volume expansion by dietary salt loading practically abolishes
tubuloglomerular feed-back (TGF) by means ofa humoral inhibitor in tubular fluid.
Elimination ofthe vasoconstrictor influence offeed-back does not, however, increase
glomerular filtration rate (GFR) and renal blood flow (RBF), implying that chronic
salt loading induces additional preglomerular vasoconstriction. This being so, the
feed-back response which, although absent in free-flowing nephrons, can still be
elicited by loop of Henle perfusion with Ringer solution, should be essentially
normal, except that nephron GFR at any loop perfusion rate should be lower than
in controls. Persistance ofRBF, GFR andnephron GFR autoregulation wouldimply
that autoregulation is achieved by a preglomerular resistance control system
independent offeed-back.
2. These hypotheses were tested by clearance and micropuncture experiments in
rats chronically fed a diet containing 40 g NaCl (kg food)-'.
3. RBF and GFR autoregulation indeed persisted, the former down to 90 mmHg
compared with 105 mmHg in controls. In controls, nephron GFR measured distally
was autoregulated down to 90 mmHg whereas that measured proximally was
autoregulated only above 105 mmHg. Inhigh-saltratsnephron GFR from both sites
was autoregulated to 90 mmHg.
4. Loop of Henle perfusion with homologous tubular fluid in high-salt rats
confirmed attenuation of feed-back. Loop perfusion with Ringer solution yielded a
response comparable to that in controls (maximal reduction of nephron GFR to
57%, compared with 56% in controls). Absolute nephron GFR atany loopperfusion
rate was lower in high-salt rats than in controls.
5. These observations confirm the initial hypotheses. Considering feed-back and
autoregulation as independent, preglomerular resistance control mechanisms,
together with elementary haemodynamic considerations, allows formulation of a
renal haemodynamics model whose quantitative predictions regarding character-
istics of RBF, GFR and feed-back control are remarkably consistent with the
literature.
* Present address and address for reprint requests: Tokyo Women's Medical College, Kidney
Center, Kawada-cho 8-1, Shinjuku-Ku, Tokyo, Japan.
Authors' names appear in alphabetical order.
474 J. M. DAVIS, D. A. HABERLE AND T. KAWATA
INTRODUCTION
Glomerular filtration rate (GFR) in normal animals is widely believed to be
controlled by the activity of the tubuloglomerular feed-back (TGF) mechanism.
Consistent with this view is the fact that the elimination of this control leads to a
substantial increase of GFR, provided the systemic blood pressure remains normal
(for literature see Schnermann & Briggs, 1985) and, further, that experimental
stimulation ofthis mechanism, for instance by proximally acting diuretics, decreases
GFR (Persson & Wright, 1982). Under conditions ofchronic volume expansion, this
mechanism is completely reset (Dev, Drescher & Schnermann, 1974; Hiiberle &
Davis, 1982; 1984) and GFR escapes from TGF control. This can beinferred fromthe
similarity ofnephron filtration rates (SNGFR) measured either byproximal ordistal
tubular fluid collection, i.e. in the presence or absence ofan operating TGF control
loop (Dev et al. 1974). The mechanism ofthis resetting phenomenon is only partially
understood. Recent studies suggested that this escape is primarily caused by the
appearance of a principle in the tubular fluid which in some manner prevents the
juxtaglomerular apparatus from responding to changes in its regulating signal, i.e.
variations of the sodium chloride concentration in the macula densa segment
(Hiiberle & Davis, 1982, 1984). However, during chronic salt loading GFR and blood
flow are not increased (Dev et al. 1974; Arendshorst & Finn, 1977; Johnston,
Bernard, Perrin, Arbeit, Lieberthal & Levinsky, 1981) as experiments in which the
control of the GFR by TGF is acutely eliminated would suggest. Provided that
observations obtained on superficial cortical nephrons are representative of the
entire nephron population, it must be concluded that chronic volume expansion
changes additional determinants ofglomerular filtration. Since chronic salt loading
isknown to increase theglomerular filtration coefficient (Schor, Ichikawa & Brenner,
1980), and assuming that TGF controls the tone of an afferent arteriolar segment
immediately adjacent to the glomerulus (Schnermann, Briggs, Kriz, Moore &
Wright, 1980) and that chronic salt loading has no significant effects on renal
filtration fraction, these considerations imply that any dilatation of the afferent
arteriole due to blockade of the macula densa TGF-sensing site must have been
compensated by another preglomerular vasoconstriction. Existence ofa 'pre-TGF'
preglomerular resistance system may also beinferredfrompressure measurements in
the preglomerular vascular bed which show a substantial pressure drop from the
renal artery up to the afferent arteriole (Kiillskog, Lindbom, Ulfendahl & Wolgast,
1976; T0nder & Aukland, 1979; BokNam, Ericson, Aberg & Ulfendahl, 1981).
The relevance of the above assumptions can be tested by the following
experiments. First, it must be established whether or not the persistance of a
'normal' GFR during chronic volume expansion is reflected by superficial cortical
nephrons. If so, the existence of a preglomerular resistance regulation should be
demonstrable, for instance during variations ofsystemic bloodpressure. Inaddition,
when the TGF response is elicited by loop ofHenle perfusion with Ringer solution,
the dependence of the SNGFR rate on perfusion rate should be similar to that in
normalratsexcept thatforagiven loop perfusion rate SNGFR should be lowerthan
in normal rats (downward shift of the feed-back curve). Finally, if, under these
circumstances, autoregulation of GFR, RBF and SNGFR persists, then this
GFR AND RBF CONTROL IN CHRONIC VOLUME EXPANSION 475
preglomerular, 'non-feed-back' resistance system can be reasonably assumed to be
the site of an autonomous autoregulation mechanism. Such a finding would have
considerable implications for the control of RBF and GFR.
METHODS
Dietary pre-treatment
Two age- and weight-matched groups of male Wistar rats (Savo-Ivanovas, Kisslegg, F.R.G.)
were used. One group was fed a control diet (0-2% sodium), the other the same diet with an
additional 4g% NaCI (1I6% sodium) for at least 10 days.
Animal preparation
Rats weighing between 180 and 320g were anaesthetized by intraperitoneal injection of
100mg Inactin per kilogram body weight (BW) (Byk-Gulden, Konstanz, F.R.G.). Body
temperature was maintained at approximately 37-5°C by a heated operating table controlled by
feed-back from a rectal thermistor thermometer. A tracheal cannula was inserted and the left
femoral artery and vein catheterized; the arteryto permit continuous recording ofblood pressure
bymeansofastrain-gauge transducer (Statham Model P23Db, Puerto Rico) andbloodsampling
as required, the vein to allow a sustaining infusion ofa 150mM-NaCl solution containing 10g%
polyfructosan (Inutest, Laevosangesellschaft, Linz, Austria) at 035ml h-1 (100g BW)-1 in
controls and 0-5ml h-1 (100g BW)' in the high-salt rats. The bladder was catheterized via a
suprapubic incision along the linea alba and the urethra and left ureter ligated. Finally, the left
kidney was exposed by a transverse flank incision, dissected free from its perirenal attachments,
laid in a Plexiglas cup, the ureter catheterized and the kidney then embedded in agar (3% in
150mM-NaCl). The renal surface was bathed and warmed (38°C) mineral oil.
After an equilibration period of 30-45min, timed urine collections were begun from the left
kidney, an arterial blood sample being taken at the end ofeach collection period.
Clearance measurement ofGFR, RBF and renalplasmaflow (RPF) autoregulation
Normal andsalt-loaded ratswerepreparedasabove. Theaortawasthencarefullydissectedfree
from surrounding attachments as far above the origin ofthe left renal artery as possible and an
adjustable screw clamp placed around it. Left renal arterial blood pressure was set at one offive
nominal pressures byadjustment oftheaortic clamp andtheinulin infusion begun. Thepressures
employedwere 140, 120, 105, 90and70mmHg;thesequencefollowedwasvariedrandomly. Inthe
control rats the spontaneous blood pressure was not sufficiently often over 140mmHg to allow
enough measurements to be made at this pressure.
Afterequilibration (30min) an arterial blood sample was taken (about 60,l) and atimed urine
collection commenced. At the end ofthe urine collection period, arenal venous blood sample was
made by puncture ofthe renal vein by a hand-held glass capillary tube (o.d., 1-5 mm), the tip of
which had been pulled and bevelled to about 35,um. The hole made in the vein sealed
spontaneously. The tip and interior ofthe capillary tube were siliconized and the collection was
madebygentlesuctionviaamouth tube. Toavoidretrograde contamination fromthevenacava,
care was taken to puncture the vein as close to the hilus as possible and to collect as slowly as
possible. Following this, a further arterial sample was taken. Blood samples were centrifuged,
haematocrit measured and the plasma portion separated, sealed and stored at -20°C until
analysis. Bloodpressurewaschangedbyadjustmentoftheclampand,afterafurtherequilibration
period, the above procedure repeated.
Measurement ofplasma volume
In aseparate series ofexperiments, plasma volume was measured in both groups by the Evans
Bluedilution technique. Afterpreparation asabove and following anequilibrationperiod ofsome
20min, a 500F1 blood sample was taken. Total protein was determined in the plasma and the
remainingplasma subsequently used toprepare thestandard concentrations ofEvansBlue. After
afurther 10min 100F1 ofa 100mgdl-' solution ofEvans Blue (E. Merck, Darmstadt, F.R.G.) in
Ringer solution was injected as a bolus i.v. Aperiod of 10min was allowed fordistribution, then
a second sample taken in which haematocrit, total protein and Evans Blue concentration were
measured.
476 J. M. DAVIS, D. A. HABERLE AND T. KAWATA
Micropuncture experiments
In vivo activity ofTGF. Rats ofboth groups were prepared asabove. Following equilibration, a
random proximal tubular segment was punctured with a micropipette (o.d., 4-6,um) containing
Ringer solution stained with 200mg% FD&C Green and buffered to pH 7-4. By means ofsmall
injections ofthis fluid, superficial segments ofthe distal convoluted tubule could be identified. If
at least two such segments were present (about 10% ofall nephrons) the most upstream one was
regarded as 'early distal' and punctured with a second oil-filled micropipette (o.d., 8,um) and a
timed, quantitative fluid collection made foratleast 3 min. Underthese circumstances flow atthe
TGF-sensing site (macula densa) is quasi-normal and, hence, the TGF control loop is intact.
Subsequently a late proximal segment of the same nephron was punctured with a further
micropipette (o.d., 12#sm) andagainatimed, quantitative collection oftubular fluidmade. Under
these circumstances the TGF control loop is interrupted. The difference between 'proximal' and
'distal' SNGFR is thus an index ofthe in vivo activity ofthe TGF mechanism.
Loop of Henle perfusion studies. In rats of both groups prepared as above the course of a
superficial proximal tubule was traced by random injection ofFD&C-stained Ringer solution as
before. Ifatleastthreesegments could beidentified upstreamfromthis 'finding'pipette, asecond
micropipette containing one oftwoperfusion fluidswasinserted into the last accessible superficial
segment and the tubule blocked by injection of paraffin wax into the penultimate segment.
Immediately thereafterthenephronwaspunctured upstream fromthewaxblockwithanoil-filled
micropipette (o.d., 12,um), the filtrate allowed to flow into this pipette and the finding pipette
removed. Perfusion ofthe loop ofHenle was then begun. The perfusion fluid was either Ringer
solution stained with FD&C green, or homologous, late proximal tubular fluid harvested
previously in the experimental animal. This method is described in detail elsewhere (Hiaberle &
Davis, 1984). Perfusion rates employed were 0, 10, 20, 30 and 40nl min-'. After allowing an
equilibration period of about 2 min, a further segment, upstream from the puncture site ofthe
finding pipette, was punctured with a micropipette (o.d., 12,um) filled with Sudan Black-stained
paraffin oil. An oil block was injected and a timed, quantitative collection oftubular fluid made.
After completion ofthe collection, theoilblockwascollected intothedownstream pipette andthe
filtrate again allowed to flow into this pipette. The perfusion rate was then changed, and the
procedurerepeated. Eachsubsequentcollectionwasmadefurtherupstreamtoavoidthepossibility
ofleakage. In any one nephron at least three perfusion rates, including 0 rate, were tested.
Autoregulation experiments. Rats from both groups were prepared as above. After selecting one
ofthreenominal bloodpressures byadjustment oftheaortic clamp (140 mmHgwasomitted since
insufficient measurements could be made at this level in the control rats, and 70mmHg was also
omitted, because of the excessively long micropuncture collection times), a random proximal
tubule was punctured and distal segments identified as above in the section on invivo activity of
TGF. Several distal-proximal paired, quantitative tubular fluid collections were made and the
blood pressure then changed. After a further equilibration period, further sample pairs were
collected.
Analyses
Clearance experiments. Urine volume was determined by weight, assuming a specific gravity of
1. Sodium and potassium concentrations in urine and plasma were determined by flame
photometry, chloride concentration by electrotitration by the Cotlove method (Chloridometer,
BuchlerInstruments, FortLee,NJ, U.S.A.), andosmolalitybyfreezingpointdepression (Roebling
Osmometer, Vogel, GieBen,F.R.G.). Inulinconcentration inplasmaandurinewasmeasuredbythe
anthrone method (Fiihr, Kaczmarczyk & Kriittgen, 1955). Haematocrit wasmeasured inallblood
samples. Plasma protein concentration was measured using a commercial kit based on the Biuret
method (Total Protein, Boehringer Mannheim, Mannheim, F.R.G.). Plasma Evans Blue was
measuredspectrophotometrically bymeasuringplasmaopticaldensityat610nmagainstaplasma
blank and comparison with a standard curve also prepared in plasma.
Micropuncture experiments. The volume ofthe tubular fluid samples was measured by injecting
the sample into an oil-filled constant-bore glass microcapillary (Microcap, 05 1l, Drummond,
IIrooma1, PA, U.S.A.) andmeasuringthelengthofthecolumnbymeansofaneyepiecemicrometer.
Inulin was determined in plasma, and urine by perchloric acid hydrolysis to fructose and
determination of the latter by the hexokinase-glucose-6-phosphate dehydrogenase method
(Renschler, 1963; Bergmeyer, Bernt, Schmidt & Stork, 1974; Bernt& Bergmeyer, 1974). Reagents
were obtained in a kit from a commercial supplier (Glucose/Fructose Kit 139 106, Boehringer
GFR AND RBF CONTROL IN CHRONIC VOLUME EXPANSION 477
Mannheim, Mannheim, F.R.G.), made up and employed according to the accompanying
instructions.
Inulin in tubular fluid samples was measured by a microadaptation of the same method. As
described in the section on in vivo activity ofTGF, chloride concentration was also measured in
tubular fluid by electrometric titration (Microtitrator Model F-25, WPI, New Haven, CT,
U.S.A.).
TABLE 1. Summary of systemic and renal function from the micropunctured kidney in control
and high-salt rats
CONTROL
GFR V
BP (ml min-' (ul min-' UNa V UK V UC1 V
(mmHg) (g KW)-') (g KW)-') (,umol min-'(gKW)-')
109+15 1-01+0-23 303+0-58 0-03+0-02 0-58+0-27 0-29+0-22
(12) (12) (12) (12) (12) (12)
Hct CProt PV BV
U/Posm (%) (g dl-') (ml(100 g BW)-1)
5-3+1-8 47-2+ 1-5 5-82+033 4-37+0-56 8-3+1-16
(12) (5) (5) (5) (5)
4 g%NaClDIET
GFR V
BP (ml min-' (,ul min-' UNa V UK V UC1 V
(mmHg) (gKW)-') (gKW)-') (#molmin-l(gKW)-')
108+10 1-06+0-18 3-82+ 1-51 0-67+0-54* 0-76+0-31 1-44+0-67*
(18) (34) (34) (34) (34) (34)
Hct CProt PV BV
U/Posm (%) (g dl-1) (ml(100 g BW)-')
6-67+ 1-81* 450+003 5-86+0-32 6-81+1-52* 12-44+2-87*
(34) (5) (5) (5) (5)
High-salt rats were fed a diet containing 4 % NaCl for at least 10 days. Abbreviations
as follows: BP, mean arterial blood pressure; GFR, glomerular filtration rate; V, urine
flow; UNaV, UK V, UC1V, urinaryexcretionof sodium,potassiumandchloriderespectively;
U/Posm, urine to plasma osmolarity ratio; Hct, haematocrit; CProt, arterial protein
concentration; PV, plasma volume; BV, blood volume; n, number ofexperiments. Data
are shown as means+s.D., with number of experiments in parentheses. * Indicates a
significant difference from the corresponding control value.
Calculations
Allflowsandvariables calculated therefrom areexpressedpergramkidneyweight (g KW). GFR
is calculated from the standard clearance expression. In the autoregulation experiments renal
plasma flow (RPF) is calculated from the inulin extraction (arterio-venous concentration
difference). Given the risk ofretrograde contamination ofthe renal venous blood samplesfrom the
vena cava, filtration fraction was calculated for each clearance period and those periods with a
filtration fraction less than 20% discarded renal blood flow is calculated from RPF and arterial
haematocrit. Plasma volume was calculated from the dilution of Evans Blue. SNGFR was
calculated as the product of tubular fluid flow rate and the tubular fluid to plasma inulin
concentration ratio. The chloride delivery to the puncture sites was simply the product oftubular
fluid flow rate and tubular fluid chloride concentration.
Statistics
Means are expressed+1 S.D. unless otherwise indicated. The significance ofdifferences between
means was assessed by Student's t test, for paired or unpaired data as appropriate. A probability
level ofless than 005 was regarded as significant.
478 J. M. DAVIS, D. A. HABERLE AND T. KAWATA
RESULTS
Clearance results
Table 1 summarizes some ofthe specific effects ofa chronic high-salt diet on renal
function, bloodpressure and blood volume. Urinary sodium chlorideexcretion, urine
osmolarity and plasma and blood volume are the only parameters to increase
compared with controls.
160
1-40
1,20
E
-E 1-00
0X80
0 80 100 120 140
B 500,_
T 400 T
EE3.00 '-
CL
z O _ _ _ __1 -A-
o 80 100 120 140
B1000 ~ -i*-~@-~;~~~_
cm 800 /
C
E 6-00
um 400
0 80 100 120 140
MABP (mmHg)
Fig. 1. Relationship between mean arterial blood pressure (MABP) and glomerular
filtration rate (GFR), renal plasma flow (RPF) and renal blood flow (RBF) in ratsfed a
control diet (@) or a diet containing 4g% NaCl (0). Data are expressed as
means±S.E.M.; * indicates a significant difference from the corresponding control
value.
Autoregulation ofrenal GFR, RBF and SNGFR
Figure 1 demonstrates the response of GFR, RPF and RBF to experimental
reduction ofmean renal arterial blood pressure. GFR in either group ofanimals is
similar at a given blood pressure, as is the relationship between these two
parameters. RPF and RBF are not significantly different in the two groups at blood
pressures of70 or over 105 mmHg. A significant difference is, however, apparent at
GFR AND RBF CONTROL IN CHRONIC VOLUME EXPANSION 479
ablood pressure of90 mmHg. This impliesthatinthehigh-saltgroup RBFandRPF
are still underthe control ofautoregulation processes atthispressure, whereas in the
controls the mechanism appears to have been exhausted at about 105 mmHg.
Autoregulation of GFR in both groups is reflected by autoregulation of GFR in
single nephrons, as shown in Fig. 2. In the salt-loaded rats SNGFR appears to be
autoregulated at blood pressures of 90 mmHg and above, regardless of the site of
measurement. In control animals, on the other hand, only the distal SNGFR was
autoregulated over the whole blood pressure range; for the proximal SNGFR the
autoregulatory mechanisms appear to be exhausted at a blood pressure of about
105 mmHg.
A Controldiet B 4gNaCl(l100g)- diet
40 (14)- (20) 4Q0
(0MAB15P) (7)) (17) MA1BP2(mm11Hg)30 (16)
C2. (10)b(
20 20
(O,0 Proximal ( PrroxiMA
z
0 Disstal n f Distal
10 10
eiaheD coto90 it10(0)o110 it12c0nann %90NC100B.P1r10xial12a0aesona
MABP (mmHg) MABP (mmHg)
Fig. 2. Relationship between nephron filtration rate (SNGFR) measured at either distal
(O, El) or proximal (@, U) sites and mean arterial blood pressure (MABP) in rats fed
either a control diet (A) or a diet containing 4g% NaCi (B). Data are shown as
means+S.E.M.; * indicates a significant difference from the corresponding distal value;
t indicates a significant difference from the corresponding value at 105mmHg. The
figures in parentheses are the number ofmeasurements.
Feed-back analysis
The above results are also reflected in a separate series of experiments in both
groups, the results ofwhich are shown in Table 2 and Fig. 4. In the salt-loaded rats
SNGFR determined at early distal and late proximal puncture sites were not
significantly different from each other and, further, were similar to distal SNGFR
values obtained in control rats. This value, however, as well as the proximal and
distal SNGFR values from the high-salt group, was significantly lower than the
proximal SNGFR in the control group. This result implies that GFR in the control
groupisunderthe control oftheTGFmechanism, whereas inthehigh-saltgroupthis
is not the case. Since, with the exception oflate proximal chloride concentration, all
other parameters are similar in both groups (Table 2), this implies that fluid
reabsorption along the nephron up to the early distal site is similar. Figure 3 shows
theresponse ofSNGFR tostimulation ofTGF byloop ofHenle perfusion with either
homologous tubularfluidorRingersolution innephronsofbothgroupsofrats. Three
480 J. M. DAVIS, D. A. HABERLE AND T. KAWATA
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GER AND RBF CONTROL IN CHRONIC VOLUME EXPANSION 481
major results are apparent. (i) As already found in the experiments above, SNGFR
in the absence ofloop perfusion was significantly higher in control rats than in the
high-saltrats. (ii) Inthesalt-loaded animals, loopperfusionwithhomologoustubular
fluidhadto beincreased to40 nl min-' before asignificant decrease ofSNGFR (from
33'0+5-5 nl min-1 (g KW)-' in the absence of loop perfusion to 25-6+6-4 nl min-'
(g KW)-'; n = 15) could be elicited. At a loop perfusion rate of20 nl min-', SNGFR
A Homologoustubularfluid B Ringersolution
_40 _40 t
3030 20 40 0 10 2030
'E
6~ ~~ *z
*
C C
cn20 /)20*
-
0<P. of.
0.0 2.0 40 0 10O 20 30 40
Vl,p (nl min-') V/P (nlmin-')
Fig. 3. Relationship between nephron filtration rate (SNGFR) measured in proximal
tubule and loop of Henle perfusion rate (V,,) in rats fed a control diet (0) or a diet
containing4g%NaCl(@). Perfusionfluidswereeitherhomologouslateproximaltubular
fluid (A)orRingersolution (B). Dataareshownasmean+S.E.M.; *indicatesasignificant
difference from the corresponding control value.
was practically identical to the value in the absence of loop perfusion (31-1 +
3.9 nl min-1 (g KW)-1; n = 9). In normal rats, loop of Henle perfusion with
homologous tubular fluid elicited significant and much greater decreases ofSNGFR
at both loop perfusion rates. The SNGFR values at loop perfusion rates of0, 20 and
40 nl min-'were 43-3+4-3 (n = 9), 26-3+4-2 (n = 6) and 22-3±3-1 nl min-' (g KW)-1
(n = 8), respectively. In summary, the feed-back response in high-salt ratsis greatly
attenuated compared with normal rats. (iii) This attenuation of the feed-back
response in the high-salt rats is no longer seen when the homologous tubular fluid is
replaced by Ringer solution as the loop perfusion fluid. At loop perfusion rates of20,
30 and 40 nl min-' SNGFR is significantly reduced to 22-5+3.5 (n = 7), 19-5+6-4
(n = 6) and 17-6+4.3 nl min-' (g KW)-1 (n = 16) respectively when compared with
the SNGFR with the loop unperfused (32-1 +7-1 nl min-' (g KW)-1; n = 16). Thus,
with Ringer solution SNGFR can be reduced to 55% ofits value in the absence of
loop perfusions compared with 78% with homologous tubular fluid.
In normal rats, loop of Henle perfusion with Ringer solution also results in a
significant decrease ofSNGFR atloop ofHenleperfusionratesof20and40 nl min-'.
The SNGFRs were 31-1+2-3 nl min-1 (g KW)-1 (n = 5) and 23-2+3-4 nl min-t
(g KW)-1 (n = 9) respectively compared with an SNGFR in the absence of loop
perfusion of41-5+6-9 nl min-' (g KW)-1 (n = 9). Thus SNGFR wasreduced to 56%
16 PHY402
482 J. M. DAVIS, D. A. HABERLE AND T. KAWATA
ofits value in the absence ofloop perfusion. This feed-back response was similar to
that observed in nephrons ofcontrol rats perfused with homologuous tubular fluid.
However, although similar in relative terms, all SNGFRs during perfusion with
Ringer solution were significantly higher in control rats than in high-salt rats. In
summary, the tubular fluid appears to differ in groups with respect to its effect upon
TGF. In contrast the effect ofRinger solution on TGF is qualitatively similar in the
two groups although all SNGFR values in the salt-loaded rats are depressed.
40
oNormaldiet
*4g% NaCI diet
.2? 3 0 -0
z
20
VXp (nlmin-')
Fig.4. Relationshipbetweennephronfiltrationrate(SNGFR) andloopofHenleflowrate
in control rats (0) and in rats fed a diet containing 4g% NaCl (0). These curves are
constructed from the data in Table 2. 0 and * represent the 'operating point' ofthe
TGF mechanism in the respective groups.
DISCUSSION
Table 1 confirms the results ofprevious studies (Hiiberle & Davis, 1982), namely
that a chronic high-salt intake induces a substantial plasma volume expansion with
practically no change in plasma protein concentration, a finding consistent with
proportional expansion of the total extracellular fluid volume (O'Connor &
Summerhill, 1982). Despite this expansion, whole-kidney GFR and RBF were not
significantly different from normal. This is in agreement with other findings on
conscious animals (Kimbrough, Vaughan, Cavey & Ayres, 1977) or animals
anaesthetized with anaesthetics other than Inactin (Arendshorst & Finn, 1977;
Johnston etal. 1981). However, the persistance ofpractically normal GFR and RPF
is atvariance with some but not all ofthose studies, in which volume expansion was
achieved by DOCA (deoxycorticosterone acetate) administration and with NaCl in
drinking water. The reason for increased RPF and GFR in some of those studies
(Schnermann, Hermle, Schmidmeier & Dahlheim, 1975; Moore & Mason, 1986) but
not in others (Sonnenberg, 1973; Hall, Guyton & Cowley, 1977; Fagard, Amery &