Renal response of chickens to infusion

of hyperosmotic sodium chloride solution””

WILLIAM H. DANTZLER Department of Pharmacology, College of Physicians and Surgeons, Columbia Universitv. New York Citv

DANTZLER, WILLIAM H. Renal response of chickens to infusion of hyperosmotic sodbm chloride solution. Am. J. Physiol. 2 I o(3) : 64o- 646. x966.-The renal response of chickens to a continuous infusion of 6% NaCl was studied. Glomerular filtration rate (GFR) decreased following infusion of 20 mEq NaCl/kg and continued to fall with continued NaCl infusion while the plasma osmolality and sodium concentration rose, Urine flow in- creased initially and did not fall below control levels until about 40 mEq NaCl/kg had been given. Urine osmolality increased, but the urine did not: become hyperosmotic. Tubular maxima for secretion of para-aminohippurate (Tm& and reabsorp- tion of glucose (Trr& decreased with GFR, suggesting that changes in GFR result from changes in the number of func- tioning nephrons. Infusion of PAH through the renal portal system did not change the relationship between TrnpYiH and GFR. TmpaH decreased more than TmG with small decreases in GFR. Possible explanations for this difference are discussed. In the absence of ability to excrete excess salt, chickens respond to a salt load with a decrease in the number of functioning nephrons, conserving water and tending to reduce plasma osmolality at the expense of excreting waste.

comparative renal physiology; intermittent nephron function; tubular transport

B IRDS, LIKE MAMMALS, can produce urine hyperosmotic to the blood. One race of Savannah sparrow, which lives in salt marshes, produces urine about four times the osmolality of the blood (14). Most other species, how- ever, have a more limited concentrating ability. The urine of the domestic chicken has a maximum concen- tration about twice the osmolality of the blood (I 0).

Thus, these animals are limited in their ability to reduce plasma osmolality by renal excretion of salt in excess of water. Although some birds (notably gulls) (x6) have salt glands which can excrete excess salt, these are lack-

Received for publication 19 -July 1965. 1 This investigation was supported by National Science Founda-

tion Research Grants GB-3309 and G-17660, and by a General Research Support Grant froxn the National Institutes of Health.

2 A preliminary report of this work was presented at the Autumn Meeting of the American Physiological Society, University of California, Los Angeles, August 23-27, 1965.

ing in the chicken. In what way, then, do these birds respond to an acute osmotic load? Korr (IO) demon- strated in one chicken that a single injection of a hy- perosmotic sodium chloride solution (about IZ mEq/kg body wt) caused a transient increase in glomerular filtra- tion rate (GFR) followed by a decrease. He stated that no decrease occurred if the animal was well hydrated. In order to determine in more detail the effects of an osmotic load upon the glomerular and tubular functions of bird kidneys, the renal response of chickens to a sus- tained infusion of a hyperosmotic sodium chloride solu- tion was investigated.

If changes in GFR occurred, I wished to determine whether these resulted from changes in filtration rate by al1 nephrons or, as in amphibians (6, I 7) and reptiles (2, 3, I I), from changes in the total number of function- ing nephrons, For this purpose the tubular maxima (Tm) for the secretion of para-aminohippurate (PAH) and the reabsorption of glucose were studied. Birds have a renal portal system, and if PAH is infused through a leg vein, it appears earlier in urine from the ipsilateral than from the contralateral kidney (2 I). For this reason, a compari- son was made of the effects of infusion through the renal portal system and infusion through the general venous system on the relationship between Tml,AI-I and GFR.

METHODS

Animals and operative procedures. Adult hens (Gallus domesticus) weighing 0.9-1.4 kg were used. They were given standard grain feed and allowed water ad lib. prior to experimental procedures. Seventeen animaIs were used in these experiments.

Animals were placed supine with outstretched wings on a specially designed bird board. The wings were taped to extensions from the board and the feet to a crossbar supported above the board. The head was placed in a black hood. No general anesthesia was used. All operations were performed under local I % lidocaine anesthesia. The right brachial vein was cannulated with PE go polyethylene tubing and the left brachial artery with PE 50 polyethylene tubing. Infusions were given through the brachial vein and blood samples collected

640

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RENAL RESPONSE OF CHICKENS TO SALT LOAD

from the brachial artery, In some animals, a PE 50 polyethylene cannula was placed in a right leg vein for infusions into the renal portal system. The ureters were cannulated by the method of Munsick, Sawyer, and van Dyke (I 3)* Small incisions were made bilaterally dorsal to the cloaca1 opening, the ureters were freed by blunt dissection, and a PI3 go polyethylene cannula was tied into each. Dead space in each cannula was about O.I- o. I 5 ml. During experiments, the board was tilted at an angle of about 45O from the table so that the bird’s head was elevated.

&naZ function stu&~. Glomerular filtration rates were estimated as inufin clearances using inulin-carboxyl- carbon 14. A priming injection of I o PC was given and the blood level maintained by a constant infusion of 0.03 &kg per min. One hour was allowed for equilibra- tion before the first collection period, A control diuresis (mean value and SE for I 37 control periods: 0.25 =t 0.007 ml/kg per min from each kidney) was produced by a constant intravenous infusion of 2.5 % rnannitol solu- tion at 0.5 ml/kg per min. Clearances were determined separately for each kidney, All collection periods were IO min in length to reduce the effect of ureteral peristalsis on the measurement of urine flow (I 9). Blood samples of 0.6-0.8 ml were collected at the midpoint of each period. Preliminary experiments showed that removal of twice the total volume of blood collected in any experiment reported in this paper had no effect on GFR.

For evaluation of TmPSfI, I .o g PAH was given as a priming injection and blood levels were maintained at about 80-130 mg/Ioo ml by a constant infusion of 4 “g/kg per min through the brachial vein with the man- ni to1 infusion. Preliminary experiments demonstrated that TrnPnH (determined at relatively constant GFR) was reached at blood levels of about 10-20 mg/Ioo ml. No self-depression of Tm pAH was seen with the blood levels maintained in these experiments. For infusion of PAH into the renal portal system, a solution of 200 mg PAH/ml was infused through the leg vein cannula at 0.06 ml/kg per min. This infusion maintained the sys- temic blood concentration at the same level as infusion through the brachial vein.

For studies involving Tmc, a priming injection of 2.5 ml/kg of 50 70 glucose in water was given through the brachial vein and a 3 % glucose infusion substituted for the 2-5 o/G mannitol infusion. This maintained a plasma concentration of about 600-800 mg/Ioo ml. At this plasma concentration, the filtered load of glucose ex- ceeded the control value for TmG unless GFR fell to less than about 35-40 % of control* It was assumed that, with a filtered load/control TmG ratio usually greater than LO, the transport system for glucose was probably saturated throughout these studies. To avoid the possi- bility of in vitro interaction between PAH and glucose (I), PAH was not added to the 3 % glucose solution until just prior to infusion.

To study the effect of an osmotic load on renal func- tion, IO mEq/kg of NaCl (as a 6 % solution) were given into the brachial vein and the control infusion replaced

mOsm

250-f l

20 o-

300-

PLASMA No+ CONC mEq/t 150- +

IO0 , :: 1 I 1 I 1 I 1 I 0 15 20 25 30 35 40 45 50

NaCl INFUSED mEq/kg BODY WEIGHT

FIG. I. Plasma osmolality, urine osmolality, and plasma sodium concentrations during sodium chloride infusion. Data are from 17 animals. Each point, except the final one, for both plasma osrnolal- ity and sodium concentration represents the mean value from more than IO determinations. The final point in each case represents the mean value from 6 determinations. Each point, except the final one, for urine osmolality represents the mean value from more than 20 determinations. The final point represents the xnean

value from g determinations. The vertical lines above and below

each point represent standard errors,

with 6 % NaCl. The infusion rate of o-5 ml/kg per min was continued and a calculated interval allowed for the NaCl solution to replace mannitol in the dead space of the infusion system before the first collection period was begun. Because of the time allowed for dead-space equil- ibration, each bird had received 15 mEq/kg body wt by the end of the first clearance period. It received an addi- tional 5 mEq/kg body wt during each ensuing clearance period,

Analytical methods. Inulin-carboxyl-carbon I 4 was de- termined in a liquid scintillation spectrometer (Packard Tri-Garb model 3224). The scintillation solution was the same as that described by Truniger and Schmidt-Nielsen (2 3). Para-aminohippurate concentrations were deter- mined by the method of Friedman, Polley, and Friedman (7) adapted for small samples using Beckman/Spinco equipment (2). Glucose determinations were carried out by the Nelson-Somogyi method also adapted for small samples using Beckman/Spinco equipment. Plasma and urine sodium concentrations were determined with a Baird flame photometer with an internal lithium stand- ard. Total osmolality of plasma and urine samples was determined with a Fiske osmometer on o.2-ml samples.

RESULTS

Effect of 6% NaCl ’ f zn usion on plasma osmolality, sodium concentration, and volume. The sodium chloride infusion produced an increase in plasma osmolality of about IO-

20 milliosmols/liter for each 5 mEq NaCl/kg given. As seen from Fig. I, the mean plasma osmolality had in-

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W. H. DANTZLER 642

I80

I60

140

I I I 1 I 15 20 25 30 35 40 45 50

NaCI INFUSED mEq/kg BODY WEIGHT

FIG. 2. Urine flow and glomerular filtration rate during sodium chloride infusion. Values are expressed as percents of the average value for 3-4 control periods in the same animal before the start: of the sodium chloride infusion. Data are from 17 animals. For both urine flow and filtration rate, each point, except the final one, represents the mean value from more than 20 determinations. The final point in each case represents the mean value from I x

determinations. The vertical lines above and below each point represent standard errors.

creased about I ;1u milliosmols/liter by the time 50 mEq NaCl/kg had been given. As would be expected, the mean increases in plasma sodium concentration (Fig. I )

accounted almost exactly for the increases in plasma osmolality. Continuation of the NaCl infusion at the same rate as the control mannitol infusion and allowance of time for equilibration prevented intravascular volume expanson from the sudden imposition of an exogenous fluid load, but the hyperosmotic solution still caused extravascular fluid to move into the vascular compart- ment. Estimation of this intravascular volume expansion from the change in plasma inulin concentration after 15 mEq NaCl/kg had been infused gave a figure of 24% with large variations (SD, 22 %I).

Effect of 6% NaCI ‘nf 2 usion on urine Jaw and glomerular and tubular functions. During the hyperosmotic saline in- fusion, the urine flow initially increased above the control level (Fig. 2). The mean increase was about 45 % after zo mEq NaCl/kg had been given. Despite considerable variation, the mean flow remained above the control level until 40 mEq NaCl/kg had been given and then proceeded to decrease steadily as the infusion was con- tinued. As long as the bird tolerated the infusion, urine flow continued, but the infusion was discontinued when the flow for a I o-min period fell to about 0.2 ml (about twice the dead space in the cannula and the minimum volume required for determination of osmolality without dilution). This point usually occurred following the in- fusion of 40-50 mEq NaCl/kg.

0

0

0.2- 9

0 0

0

0 1 :: I 1 r I I I I

0 I5 20 25 30 35 40 45

NaCl INFUSED

mEq/kg BODY WEIGHT

FIG, 3. Urine flow and glomerular filtration rate during sodium chloride infusion for a representative animal (chicken ~5, right kidney). The control. points (o NaCl/kg infused) represent mean values from 4 determinations. The vertical lines above and below each point represent standard errors. All other points represent single determinations.

The glomerular filtration rate did not follow the pat- tern shown by the urine flow (Fig. 2). The mean control value was I .23 & 0.04 ml/kg per min (SE on I 37 deter- minations). After the birds had received 15 mEq NaCl/kg, the mean filtration rate was unchanged from the control level. As the infusion of NaCl continued, however, the GFR decreased, reaching a mean value of less than 40 % of the control after the infusion of 45-50 mEq NaCl/kg. This pattern of changes in urine flow and filtration rate is illustrated by the results from a repre- sentative experiment shown in Fig. 3.

In accord with the pattern of decreasing filtration rate in the presence of high urine flow, the inulin/plasma (U/P) ratio (Fig. 4) tended to decrease from 5.45 =t 0.20 (SE on 137 determinations) to a low of 3.42 + 0.30 (SE on 26 determinations) following infusion of 30 mEq NaCl/kg. As both flow and filtration fell with continued hyperosmotic infusion, the inulin U/P approached the control level.

The total osmolality of the urine increased, but, in the presence of a severe osmotic diuresis, the tubular reabsorption of water did not. Thus, as can be seen from Fig. I, the urine-to-plasma osmolality ratio did not change significantly during most of the sodium chloride infusion. After the infusion of 45-50 mEq NaCl/kg, when urine flow and filtration rate were very low, there was greater variation in urine osmolality and a tendency for some samples to equal or slightly exceed the plasma osmolality. At this low flow, the tubular reabsorption of water increased despite the presence of a severe osmotic load. However, in only 3 periods (out of 210) during the hyperosmotic infusion did the osmolar urine-to-plasma ratio exceed I. 2.

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RENAL RESPONSE OF CHICKENS TO SALT LOAD 643

TABLE I. %pAH before and during glucose infusion

I f

7,O i

5.0

INULIN

!

9 i

P P

P

u'p 3.0 p 3 P 8

25 NaCl INFUSE0

mEq/kq BODY WEIGHT

FIG. 4. Inulin U/P ratios and sodium clearances during sodium chloride infusion. Data are from 17 animals. Sodium clearance is shown as percent of inulin clearance. Each point, except the final one, for sodium clearance represents the mean value from more than 15 determinations. The final point represents the mean value from 6- determinations. Each point, except the final one, for the inulin U/P ratios represents the mean value from more than 20

determinations. The final point represents the mean value from IO

determinations.

As might be expected during the infusion of a salt load, the mean percent of filtered sodium reabsorbed by the renal tubules decreased. Thus, as shown in Fig. 4, the mean sodium clearance increased from about g % of that filtered to about 30 75, but there was a tendency for this to decrease again at the very lowest urine flows.

Intermittent nephron function. It was first demonstrated by Ranges et al. (15) that the Tm for glucose could be studied to determine whether changes in GFR resulted from changes in filtration by each nephron or from changes in the number of functioning nephrons. If changes in GFR resulted from changes in the amount

filtered by each nephron, but all continued to function, the Tm for glucose would not be expected to change. If, however, changes in GFR resulted from changes in the number of functioning nephrons, the Tm would be ex- pected to vary directly with GFR. Studies on frogs (6, 17) showed that the Tm for PAH, a substance secreted by the tubules, varied with GFR in the same fashion as the Tm for glucose, a substance reabsorbed by the tu- bules. In the present study a comparison of variations in the Tm of both substances was made.

Houck (8) reported that in dogs high plasma glucose levels may suppress the maximal tubular transport of PAH by as much as 23%. In two chickens in which TmPAW could be measured at comparable glomerular filtration rates before and during glucose infusion, there was no evidence of significant depression of TmpAH (Table I). In one case, TmpAH: even tended to increase slightly after the glucose infusion was begun.

The Tm for both PAH and glucose, whether given

TmpAH Before Glucose, T~PAXI During Glucose, Chicken No. Kidney mg/kg per min mg/kg per min

9 Right I .08 & 0.18 (4) 1.50 * 0.24 (3) Left 1.62 + 0.11 (3) 1.58 A 0.16 (3)

16 Right 1.71 zt 0.06 (3) E .65 h 0.06 (3) Left 1.93 •t 0.09 (3) I .60 =k 0.02 (3)

Figures are means =I= SE.

singly or together, decreased with GFR, indicating that nephrons frunction intermittently. This relationship for both substances is illustrated for representative animals in Fig. 5. As can be seen, the slope for TmG vs. GFR is steeper than that for Tm PAH VS. GFR. Tables 2 and 3 show the coefficients of correlation and the slopes for TmPAH and Tmc vs. GFR for all animals studied. There is a high correlation between GFR and the Tm for both PAH and glucose for all animals. The mean coefficient

of correlation for Tm PAH VS. GFR is +o.g47 & 0.006

(SE on 25 determinations); for TmG vs. GFR, +o.g8o & 0.005 (SE on I 4 determinations). There is also no signifi- cant difference in the correlation of TmpAH with GFR if PAH is given via leg vein rather than via wing vein. The mean coefficient of correlation is +o.g48 =t 0.007 (SE on 17 determinations) for the brachial vein route; + 0.946 =t: 0.008 (SE on 8 determinations) for the leg vein route,

There is significant difference ( P < 0.001) between the mean slopes for TmpAH vs. GFR and TmG vs. GFR. The mean slope for the former relation is + I .54 j_ o. I 7 (SE on 25 determinations); for the latter, + 3.81 =t: 0.24 (SE on 14 determinations). These figures for the slopes of the curves are also numerically equivalent to the mean values in milligrams per kilogram per minute for TmpArr and TmG, respectively, at a filtration rate of I ml/kg per mm.

In Fig. 6, TmpAH and TmG are plotted as percents of the control values against the quantity of sodium chloride infused. It can be seen, by comparing this figure with the corresponding plot for changes in GFR (Fig. 2), that the mean decreases in TmG follow very closely the mean decreases in GFR. On the other hand, with small de- creases in GFR, the mean decreases in TmpAH tend to be greater than those for Tm G+ When filtration reaches low levels, the mean percen tage d TmPAH approxima te each other.

.ecreases in TmG and

DISCUSSION

In the present study, a hyperosmotic sodium chloride infusion produced a marked decrease in glomerular filtration rate. This occurred early during the infusion despite a definite increase in urine flow. The decrease in filtration rate prior to a decrease in urine flow cannot be the result of dead space errors. With a falling inulin U/P ratio, any dead space error would only have tended to reduce the apparent rate at which GFR decreased. The initial increase in urine flow would appear best ex- plained by the effect of a hyperosmotic sodium chloride load on the tubular reabsorption of ions and water.

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‘Mr. 13. DANTZLER

FIG. 5. Rel ationship between TrnpaH and TmG and GFR for representative animals (chickens 20 and zr, respectively).

7.0 -I 6.0-

0 1 1 1 1.0 zoo 3.0

GFR ml/kq/min

TABLE 2 l Carre~ation coeficients and slopes for relationshib between TmpAH and GFR

1

Chicken No.

5

7

9

II

I2

16

I7

23

26

Kidney

Right Left

Left Right Left

Right Left

Right Left

Right Left

Right Left

Right Left

Right Left

Right Left

Right Left

Right Left

Right Left

Route of Infusion

Wing vein

Wing vein

Wing vein

Wing vein

Wing vein

Wing vein

Wing vein

Wing vein

Wing vein

Leg vein

Leg vein

Leg vein

Leg vein

Coeff. of Correlation

+o.gQ +o * go0

lto.914

+o -897 -to 4 942

-to .g83

+0*994

+o.g@ +o ,986

+o ,968 +0.961

+o-997 +0.921

+o.gQ t-o.904

+o.g28

+0.8g7

+o.g84 +o ,967

+o.gy)

+o-937

+o .gq

+a*935

+o.g6z

+o-943

Slope

+I .70 +I. 18

+I .71

+r .I0

+I .32

+3 -99 +4-75

+I 057

+I .g2

+0.516 +I .06

+I .40 +I *I3

+I *59 +I .52

+0.781

+0*635

+I .58

+I -59

+o ,972 +o.g&

+I * ‘9 +I .23

+I .8g +I .82

These findings differ from those of Korr (I o)* He stated that following an acute infusion of about I 2 mEq NaCl/kg in one chicken the GFR doubled and then fell steadily. Urine flow paralleled GFR. However, his data show that the GFR and urine flow were increasing rapidly before the salt load was given, and it is difficult to interpret the effect of the experimental procedure.

As pointed out by Kerr, dead space errors might have been responsible for rapid changes in GFR with his col- lection procedures. If the increase in GFR was real, it probably resulted from the sudden expansion of the intravascular volume by the addition of an exogenous fluid load. In the present study, increases in filtration rate did occur initially in some animals, but the mean value for all animals showed no increase, It appears probable that limitation of intravascular volume expan- sion by continuing’ the sodium chloride infusion at the same rate as the mannitol infusion tended to prevent initial increases in filtration rate.

The glomerular filtration rate decreased as plasma osmolality and sodium concentration rose. Although no depression of filtration rate had been demonstrated in chickens with injections of arginine vasotocin (Ig), the natural antidiuretic principle in birds (x3), or avian neurohypophysial extracts (W. H. Sawyer and W. H. Dantzler, unpublished observations), it still appeared possible that the response to a salt load might result from a continuous release of the peptide. Several pre- liminary experiments with sustained infusions of synthetic arginine vasotocin in an attempt to mimic a continuous release (total dose: 5,ooo-9,500 mU) showed no con- sistent depression of filtration rate. These doses greatly exceeded the amount contained in the chicken neuro- hypophysis (about 4oo xnU) (I 3). These results, together with those of Skadhauge (I g), thus make it unlikely that the avian glomerular filtration rate is controlled pri- marily by arginine vasotocin.

The evidence from the studies of Tm for glucose and PAH tends to support the concept that changes in filtra- tion rate in chickens, like those in amphibians (6, I 7) and reptiles (2, 3, I I), result from changes in the num- ber of functioning nephrons. Although it is possible that all nephrons may continue to function and that the changes in Tm and GFR result from a marked reduction in filtration in some of the nephrons and a drastic redis- tribution of flow throughout the nephron population, this appears to be a more complicated explanation of the data. Therefore, in the rest of the discussion, I shall assume that the simpler, classical concept of Ranges et al. (15), that variation of Tm with GFR reflects intermit- tency of nephron function, is the more likely hypothesis.

The correlation between TmPAH and GFR does not change significantly when PAH is infused by leg vein rather than by wing vein. Nor is this correlation different for the kidney on the side of the leg vein infusion when compared with the contralateral kidney. This suggests that, as long as the plasma concentration of PAH ex- ceeds the value for Tm, the distribution to the tubules during changes in GFR is not altered by the route of infusion.

The observation that TmPAH, regardless of the route of infusion, tends to decrease more rapidly than GFR or TmG with small decreases in GFR is of considerable interest in relation to tubular function in birds. Recent micropuncture studies on rats (4) have strengthened the assumption that Tm G reflects the functioning tubular

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RENAL RESPONSE OF CHICKENS TO SALT LOAD 645

TABLE 3. Correlation coeficients and shpes fur relationship befween TmG and GFR

filtration has ceased may also lead to an increase in back-diffusion and a depression of TmpAH dispropor- tionate to the number of functioning nephrons. In either case, at low filtration rates where few nephrons are func- tioning, it might be expected that the percentage de- crease in Tm PAH would approach the percentage de- crease in filtration. In the present study this does occur.

The tubular cells of avian nephrons have a dual blood supply, derived in part from the renal portal system and in part from the postglomerular arterioles. The venous blood from the former and the arterial blood from the latter are mixed in the peritubular capillaries. A valvular arrangement (20, 2 I) determines the extent to which venous return from the legs enters or bypass& the renal portal system. A decrease in glomerular filtration rate with rising blood osmolality and sodium concentration probably results from a decrease in blood supply to the nephrons. When this occurs, the blood supply to the tubules could decrease more rapidly than the blood supply to the glomeruli if some of the returning venous blood bypassed the renal portal system. In this case, the maximum tubular transport of PAH might be reduced more rapidly than the glomerular filtration rate. Such a reduction could result from the direct effect of a reduced

Chicken X0. Kidney

5 Right

Coeff. of Correlation

+o.g8g

Slope

+2.66

9 Right +0*994 +4-29 Left +o-937 +4*24

I5 Right Left

+0*949 +3 .o8 +o.g+ +3.11

16 Right +o.ggo +o.g@ +o.gg* +o .g8g

-t4*96

+4,48

+3.00

+* .99 =7 Right

Right Left

-to*997 +3~6

+o-994 f3.37

Left -to .gg6 +o.g8o

+3,72

+5.62 +4.66

Right Left +o.970

blood SU pply on the transport system. from a reduction below the tubular

I t might maximi

also result n the Am i

quantity of PAH actually reaching the cells despite plasma concentrations apparently well above Tm.

Leyssac (12) suggested that glomerular filtration may be controlled by the reabsorption of sodium. It is possible, in the present study, that diminished sodium reabsorp- tion during the sodium chloride load could have led to an increase in intraluminal pressure and a net decrease in filtration pressure. It is also possible that decreasing sodium reabsorption could have influenced the transport of glucose and PAH. However, although the mean value for sodium reabsorption decreased during the sodium chloride infusion, there was no decrease in a few animals and a slight increase in one animal. This occurred de- spite marked decreases in GFR, TmpAH, and TmG in these animals. Thus, it appears unlikely that a decrease in tubular reabsorption of sodium could be solely respon- sible for the observed changes in GFR and tubular trans- port of glucose and PAH.

Of what imfiortance to birds are thg obserued changes in renal function? Kerr’s work (IO) and the present study showed that chickens tolerate increases in plasma osmolality poorly. I f blood osmolality was increased too rapidly or a hyperosmotic infusion continued beyond the point where the urine flow became low (about 0.02 ml/kg per min), the animals died. This occurred despite some in- crease in intravascular volume produced by a hyper- osmotic infusion. It appears that, when subjected to severe dehydration or a salt load, the domestic fowl must prevent or slow the resulting rise in blood osmolality. This could be accomplished by the production of hyper- osmotic urine, the reduction of glomerular filtration rate, or the extrarenal excretion of ions. However, the domestic fowl has never been observed to produce a

of :: I I T I I I I 1

I5 25 30 35 50

NaCI INFUSED

mEq/kg BODY WEIGHT

FIG. 6. Tml>,jH and Tmc, during sodium chloride infusion. Val- ues are expressed as percents of the average value for 3-4 control periods in the same animal before start of the sodium chloride infusion. Data are from 16 animals. Each point, except the final one, for Trnp~~~l~ represents the mean value from more than 15 determinations. The final point represents the mean value from g determinations. Each point for TmG represents the mean value from more than IO determinations except the first, sixth, and final points which represent mean values from 7, g, and 4 determina- tions, respectively. The vertical lines above and below each point represent standard errors.

mass, but have suggested that TmpAH is unrelated to tubular mass (5). Instead, TmpaH appears to depend in part on the intraluminal concentration of PAH and the rate of flow through the tubules. If a number of glomeruli cease functioning as GFR falls, the cessation of flow and increased intr #alumi nal nephrons mav cause ad

concentr #ation of PAH in these apparen t TmI’AH which ecrease in

is disproportionate to the actual functioning tubular mass. Furthermore, there is evidence in mammals that back-diffusion of PAH across the tubular epithelium occurs ( 18)~ The increased intraluminal concentration in that portion of the nephron population in which

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646

urine with an osmolality more than twice that of the blood (IO). With a limited ability to excrete ions in a concentrated urine and without an extrarenal route of ion excretion, these animals can only retard increases in blood osmolality by reducing the number of functioning nephrons and conserving water at the expense of excret- ing waste. Kerr (I o) observed a 50 % decrease in filtra- tion rate in one chicken dehydrated for 48 hr. And Hughes 0 even found that gulls, birds with actively functioning salt glands, showed some decrease in filtra-

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tion rate during a salt load. By decreasing the number of functioning nephrons during a salt load or dehydration, birds differ from mammals, which can produce a highly concentrated urine, and closely resemble amphibians (17) and reptiles (2, 3, I I), which cannot.

The author thanks Professor Wilbur I-I Sawyer for his en-

couragement and support during the course of this study. The author also expresses his appreciation to Margot Acosta and

William Sullivan for their able technical assistance.

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