AMERICAN JOURNAL OF PHYSIOLOGY Vol. 231, No. 4, October 1976. Printed
in U.S.A.
Renal hydrogen ion secretion after release of unilateral ureteral KHAMNUNG THIRAKOMEN, NICHOLAS AND NEIL A. KURTZMAN Sections of Nephrology, Univers@y of Illinois Veterans Administration West Side Hospital,
KOZLOV, Abraham Chicago,
THIRAKOMEN, KHAMNUNG, NICHOLAS KOZLOV, JOSE A. L. ARRUDA, AND NEIL A. KURTZMAN. Renal hydrogen ion secretion after release of unilateral ureteral obstruction. Am. J. Physiol. 231(4): 1233-1239. 1976. -The effect of 24 h of unilateral ureteral obstruction on HCO, reabsorption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO, loading was significantly higher in the EK as was maximal HCO, reabsorption. Saline loading depressed HCO, reabsorption to the same degree in both kidneys. Urinary Pco,, during HCO, loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na,SO, administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO, loading and Na,SO, administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney.
obstruction JOSE
A. L. ARRUDA,
Liizcoln School of Medicine, Illinois 60612
and
METHODS
Twenty-eight experiments were performed on 28 female mongrel dogs. Twenty-four hours prior to the study, the dogs were anesthetized with sodium pentobarbital, 30 mg/kg iv. Through a suprapubic incision, the right ureter was identified and ligated completely. The incision was then closed and dogs were returned to their cages. Twenty-four hours later, the dogs were again anesthetized with sodium pentobarbital (30 mg/ kg iv); light anesthesia, as judged by preservation of the cornea1 reflexes, was maintained by subsequent small doses. An endotracheal tube was inserted and connected to a Bird respirator; arterial CO, tension was kept between 35 and 45 mmHg by appropriate manipulation of the respirator. An arterial catheter was used to obtain arterial blood and to record and monitor blood pressure. A femoral vein catheter was used for infusions. Using a suprapubic incision, both ureters were identified and cannulated. Saline (0.9%) containing [1251]iothalamate (115 ,&i/liter) was administered at 0.6 ml/min throughout each experiment as a marker of GFR. Saline containing 4 mg/ml of p-aminohippurate (PAH) was also administered at 0.5 ml/min throughout each experiment. An equilibration period of at least 60 min was allowed before any collection was started. Collection periods were started only when urine flow of both kidacid excretion; HCO, reabsorption; ureteral obstruction neys had stabilized. Collection periods were 10 min in duration except in group II in which collections were of 30 min duration. All blood samples collected were immediately replaced with an equal volume of 0.9% saline. THE EFFECTS OF unilateral ureteral obstruction (UUO) on renal function have been studied extensively (5, 6, 8, Urinary losses also were replaced with 0.9% saline. 11, 14, 22, 25, 30). After release of UUO, the postobGroup IA- bicarbonate loading. After two control periods, 11 dogs were infused with 0.9 M NaHCO, at strutted kidney exhibits a reduced glomerular filtration rate (GFR), renal plasma flow (RPF), and concentrating varying rates to maintain a plasma HCO, concentration ability as well as enhanced phosphate reabsorption and between 30 and 40 meq/liter. Clearance periods with decreased sodium reabsorption (5, 6, 8, 22). Studies in HCO, concentration outside the range of 30-40 meq/liter man and rats have also demonstrated that the postob- were not used. After four clearance periods, the dogs strutted kidney has impaired hydrogen ion secretion (6, were infused with 0.9% saline (10% body wt) for 100 27). Sodium reabsorption and hydrogen ion secretion are min. factors known to control bicarbonate reabsorption (18). Group IB - bicarbonate loading plus phosphate infuOne would, therefore, expect a different pattern of bi- sion. Six dogs were infused with 0.9 M NaHCO, in order to achieve a maximally alkaline urine (urine pH 7.8carbonate reabsorption in the postobstructed kidney 8.0). After three clearance periods, isotonic buffered (EK) as compared to the contralateral kidney (CK). Accordingly, we studied the effects of 24 h of UUO on phosphate solution (Na,HPO, - NaH,PO, in a molar bicarbonate rea,bsorption and urinary acidification. ratio of 4:l) was infused at a rate of approximately 0.09 1233
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (130.070.008.131) on October 3, 2018. Copyright © 1976 American Physiological Society. All rights reserved.
1234
THIRAKOMEN,
mg/kg per min, and three to four clearance collections were obtained. Group II- sodium sulfate infusion. Six dogs were treated with deoxycorticosterone acetate (DOCA) 5 mg subcutaneously 12 and 2 h before the study. After two control periods, 4% Na,SO, was infused for 2 h at a rate adjusted to deliver 0.78 mg of Na,SO,/kg per 2 h. Four 30-min periods were obtained during the infusion of Na,SO,. Group III- renal blood flow distribution and plasma renin activity. In five dogs blood was drawn from both renal veins and the inferior vena cava for plasma renin activity (PRA) determination. Blood was obtained from the inferior vena cava by an indwelling catheter and from the renal veins by direct puncture of the renal veins with a 25gauge needle. Three blood collections were drawn; one before the release of the ureteral obstruction, a second sample after 1 h of release of the ureteral obstruction, and the third after 10% body wt expansion with 0.9% saline (as in group 1). Catheters were placed in the left ventricle (for microsphere injection) and in the femoral artery for blood sampling. Radioactive microspheres (MS) 15 t 5 pm in size labeled with s5Sr or 141Ce were injected into the left ventricle within 10 s; a total amount of 15 &i (400,000 MS) was injected. Immediately after the administration of the microspheres, femoral arterial blood was drawn at a constant rate using a Sage pump over a l-min period, and the volume withdrawn was noted. The first set of microspheres (s5Sr) was injected 1 h after the release of the ureteral obstruction. The second set of microspheres (14Ce) was injected after 100 min of volume expansion with 0.9% saline. At the end of each experiment, both kidneys were removed. Glomerular filtration rate, blood and urinary electrolyte determinations, and statistical analyses were performed as previously reported (18). Titratable acidity and ammonium were measured by the Formalin titrimetic method as described by Cunarro and Weiner (9). Plasma renin activity was measured by radioimmunoassay as described by Haber et al. (12). TABLE
1. Bicarbonate Urine
reabsorption
Flow
GFR
after unilateral
RPF (C,,,)
Filtration Fraction
mllmin EK C
1.0 P < 2.2 P < 7.5
BL VE CK C BL VE P values C BL VE Values
comparing
are means
I!I 0.2 0.001 2 2.3 0.001 k 1.2
17.1 + 2.70 P < 0.05 20.1 + 2.90 P < 0.05 23.8 +- 3.70
54.7 IL 12.6 NS 50.5 + 7.5 NS 63.4 + 11.0
0.31 It 0.03 P < 0.02 0.40 2 0.02 NS 0.38 k 0.03
0.9 I!I 0.2 P -=c0.001 3.4 + 0.5 P < 0.001 9.6 + 1.0
33.6 + 3.60 NS 32.4 + 3.70 NS 33.7 in 4.40
92.1 + 17.6 NS 87.9 2 11.0 NS 103.8 + 16.8
0.36 ‘- 0.03 NS 0.37 + 0.03 NS 0.32 2 0.03
the two control, NS NS NS + SE. C, control
the two bicarbonate-loading, P < 0.01 NS P < 0.05 P < 0.02 NS NS period;
BL, bicarbonate
period;
AND
KURTZMAN
RESULTS
Table 1 shows a summary of data obtained in the bicarbonate-loaded dogs. During control and bicarbonate loading, GFR was significantly lower in the experimental kidney than in the control kidney. Volume expansion led to a significant increase in GFR in the EK but not in the CK; after volume expansion there was no significant difference in GFR of the two kidneys. RPF was lower in the EK than in the CK, but this difference was significant only during bicarbonate loading. After volume expansion, RPF did not change significantly in either the CK or the EK. There was no significant difference in filtration fraction between the CK and the EK. During control, fractional sodium excretion, although slightly greater in the EK was not significantly different from the CK (3.3 t 1.20 vs. 1.9 t 0.50). Figure 1 plots bicarbonate reabsorption against plasma bicarbonate concentration during bicarbonate loading and volume expansion. As can be seen during bicarbonate loading, bicarbonate reabsorption is significantly higher in the EK than in the CK (2.59 vs. 2.28 meq/lOO ml of GFR, P < 0.01; EKy = 3.05 - 0.01~ and CKy = 1.31 + 0.03x.) The 95% confidence limits do not overlap. Figure 2 plots bicarbonate reabsorption against fractional chloride excretion. During bicarbonate loading, bicarbonate reabsorption for any given fractional chloride excretion was higher in the EK than in the CK. Volume expansion (Figs. 1 and 2) led to a significant depression of bicarbonate reabsorption in both kidneys. After volume expansion, there was no significant difference in bicarbonate reabsorption between the EK and obstruction
Plasma HCO,
HCO, Reabsorption
meqlliter
meqlliter GFR
(C,,/GFR) x 100
(C,,,/GFR) x 100
%
UKV peqlmin
UPH per 100 ml GFR
upco* mmHg
19.4 I!z 0.80 P -=I 0.001 25.9 * 0.70 P < 0.001 18.9 + 1.20
3.4 It 1.40 NS 4.9 2 1.00 P < 0.001 22.9 + 2.10
7.9 ?I 2.00 P < 0.01 21.0 + 4.00 P < 0.001 39.6 IL 4.60
64.2 + 9.40 P < 0.01 103.5 + 11.50 NS 115.6 + 9.30
7.14 + 0.06 P < 0.001 7.80 + 0.03 P < 0.01 7.69 2 0.03
38.3 2 2.00 NS 42.3 +- 2.10 P < 0.05 39.2 + 1.50
19.8 + 0.80 P < 0.01 22.8 +- 0.60 P < 0.001 17.7 + 1.00
2.1 -t 0.79 P < 0.01 6.1 rf 1.50 P < 0.001 23.8 2 1.70
20.9 + 4.10 P < 0.001 42.3 -t 5.30 P < 0.05 56.4 -t 1.90
78.2 + 6.60 P < 0.001 162.5 2 10.00 NS 175.9 2 11.20
6.84 k 0.10 P -=I 0.001 7.80 + 0.03 P < 0.01 7.69 + 0.02
66.0 r+ 6.60 NS 67.8 + 6.20 P < 0.01 45.7 + 2.30
periods NS P < 0.01 NS
NS NS NS
P < 0.01 P < 0.01 P < 0.01
NS P < 0.001 P < 0.001
P < 0.05 NS NS
P < 0.001 P < 0.001 P < 0.05
and the two volume-expanded NS NS NS loading
ARRUDA,
Renal plasma flow (RPF) in group I was estimated by measuring the clearance of PAH. Total renal blood flow (TRBF) in group 111 was measured as previously described (1); the methods of sectioning the kidneys and calculating distribution of renal blood flow were identical to those reported by Bay et al. (3). Data are presented as mean plus or minus standard error of the mean.
ureteral
20.2 k 0.80 P < 0.001 32.7 rt 0.43 NS 32.9 2 0.43
KOZLOV,
VE, volume-expanded
period.
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (130.070.008.131) on October 3, 2018. Copyright © 1976 American Physiological Society. All rights reserved.
H+
SECRETION
AFTER
URETERAL
Bicorb
Loading
Vol Expansion 0 Experimental Kidney o Control Kidney 0
3.0 .
1
A
0 l
2.6
0
0
0
00.
0
p
in U.S.A.
Renal hydrogen ion secretion after release of unilateral ureteral KHAMNUNG THIRAKOMEN, NICHOLAS AND NEIL A. KURTZMAN Sections of Nephrology, Univers@y of Illinois Veterans Administration West Side Hospital,
KOZLOV, Abraham Chicago,
THIRAKOMEN, KHAMNUNG, NICHOLAS KOZLOV, JOSE A. L. ARRUDA, AND NEIL A. KURTZMAN. Renal hydrogen ion secretion after release of unilateral ureteral obstruction. Am. J. Physiol. 231(4): 1233-1239. 1976. -The effect of 24 h of unilateral ureteral obstruction on HCO, reabsorption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO, loading was significantly higher in the EK as was maximal HCO, reabsorption. Saline loading depressed HCO, reabsorption to the same degree in both kidneys. Urinary Pco,, during HCO, loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na,SO, administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO, loading and Na,SO, administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney.
obstruction JOSE
A. L. ARRUDA,
Liizcoln School of Medicine, Illinois 60612
and
METHODS
Twenty-eight experiments were performed on 28 female mongrel dogs. Twenty-four hours prior to the study, the dogs were anesthetized with sodium pentobarbital, 30 mg/kg iv. Through a suprapubic incision, the right ureter was identified and ligated completely. The incision was then closed and dogs were returned to their cages. Twenty-four hours later, the dogs were again anesthetized with sodium pentobarbital (30 mg/ kg iv); light anesthesia, as judged by preservation of the cornea1 reflexes, was maintained by subsequent small doses. An endotracheal tube was inserted and connected to a Bird respirator; arterial CO, tension was kept between 35 and 45 mmHg by appropriate manipulation of the respirator. An arterial catheter was used to obtain arterial blood and to record and monitor blood pressure. A femoral vein catheter was used for infusions. Using a suprapubic incision, both ureters were identified and cannulated. Saline (0.9%) containing [1251]iothalamate (115 ,&i/liter) was administered at 0.6 ml/min throughout each experiment as a marker of GFR. Saline containing 4 mg/ml of p-aminohippurate (PAH) was also administered at 0.5 ml/min throughout each experiment. An equilibration period of at least 60 min was allowed before any collection was started. Collection periods were started only when urine flow of both kidacid excretion; HCO, reabsorption; ureteral obstruction neys had stabilized. Collection periods were 10 min in duration except in group II in which collections were of 30 min duration. All blood samples collected were immediately replaced with an equal volume of 0.9% saline. THE EFFECTS OF unilateral ureteral obstruction (UUO) on renal function have been studied extensively (5, 6, 8, Urinary losses also were replaced with 0.9% saline. 11, 14, 22, 25, 30). After release of UUO, the postobGroup IA- bicarbonate loading. After two control periods, 11 dogs were infused with 0.9 M NaHCO, at strutted kidney exhibits a reduced glomerular filtration rate (GFR), renal plasma flow (RPF), and concentrating varying rates to maintain a plasma HCO, concentration ability as well as enhanced phosphate reabsorption and between 30 and 40 meq/liter. Clearance periods with decreased sodium reabsorption (5, 6, 8, 22). Studies in HCO, concentration outside the range of 30-40 meq/liter man and rats have also demonstrated that the postob- were not used. After four clearance periods, the dogs strutted kidney has impaired hydrogen ion secretion (6, were infused with 0.9% saline (10% body wt) for 100 27). Sodium reabsorption and hydrogen ion secretion are min. factors known to control bicarbonate reabsorption (18). Group IB - bicarbonate loading plus phosphate infuOne would, therefore, expect a different pattern of bi- sion. Six dogs were infused with 0.9 M NaHCO, in order to achieve a maximally alkaline urine (urine pH 7.8carbonate reabsorption in the postobstructed kidney 8.0). After three clearance periods, isotonic buffered (EK) as compared to the contralateral kidney (CK). Accordingly, we studied the effects of 24 h of UUO on phosphate solution (Na,HPO, - NaH,PO, in a molar bicarbonate rea,bsorption and urinary acidification. ratio of 4:l) was infused at a rate of approximately 0.09 1233
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (130.070.008.131) on October 3, 2018. Copyright © 1976 American Physiological Society. All rights reserved.
1234
THIRAKOMEN,
mg/kg per min, and three to four clearance collections were obtained. Group II- sodium sulfate infusion. Six dogs were treated with deoxycorticosterone acetate (DOCA) 5 mg subcutaneously 12 and 2 h before the study. After two control periods, 4% Na,SO, was infused for 2 h at a rate adjusted to deliver 0.78 mg of Na,SO,/kg per 2 h. Four 30-min periods were obtained during the infusion of Na,SO,. Group III- renal blood flow distribution and plasma renin activity. In five dogs blood was drawn from both renal veins and the inferior vena cava for plasma renin activity (PRA) determination. Blood was obtained from the inferior vena cava by an indwelling catheter and from the renal veins by direct puncture of the renal veins with a 25gauge needle. Three blood collections were drawn; one before the release of the ureteral obstruction, a second sample after 1 h of release of the ureteral obstruction, and the third after 10% body wt expansion with 0.9% saline (as in group 1). Catheters were placed in the left ventricle (for microsphere injection) and in the femoral artery for blood sampling. Radioactive microspheres (MS) 15 t 5 pm in size labeled with s5Sr or 141Ce were injected into the left ventricle within 10 s; a total amount of 15 &i (400,000 MS) was injected. Immediately after the administration of the microspheres, femoral arterial blood was drawn at a constant rate using a Sage pump over a l-min period, and the volume withdrawn was noted. The first set of microspheres (s5Sr) was injected 1 h after the release of the ureteral obstruction. The second set of microspheres (14Ce) was injected after 100 min of volume expansion with 0.9% saline. At the end of each experiment, both kidneys were removed. Glomerular filtration rate, blood and urinary electrolyte determinations, and statistical analyses were performed as previously reported (18). Titratable acidity and ammonium were measured by the Formalin titrimetic method as described by Cunarro and Weiner (9). Plasma renin activity was measured by radioimmunoassay as described by Haber et al. (12). TABLE
1. Bicarbonate Urine
reabsorption
Flow
GFR
after unilateral
RPF (C,,,)
Filtration Fraction
mllmin EK C
1.0 P < 2.2 P < 7.5
BL VE CK C BL VE P values C BL VE Values
comparing
are means
I!I 0.2 0.001 2 2.3 0.001 k 1.2
17.1 + 2.70 P < 0.05 20.1 + 2.90 P < 0.05 23.8 +- 3.70
54.7 IL 12.6 NS 50.5 + 7.5 NS 63.4 + 11.0
0.31 It 0.03 P < 0.02 0.40 2 0.02 NS 0.38 k 0.03
0.9 I!I 0.2 P -=c0.001 3.4 + 0.5 P < 0.001 9.6 + 1.0
33.6 + 3.60 NS 32.4 + 3.70 NS 33.7 in 4.40
92.1 + 17.6 NS 87.9 2 11.0 NS 103.8 + 16.8
0.36 ‘- 0.03 NS 0.37 + 0.03 NS 0.32 2 0.03
the two control, NS NS NS + SE. C, control
the two bicarbonate-loading, P < 0.01 NS P < 0.05 P < 0.02 NS NS period;
BL, bicarbonate
period;
AND
KURTZMAN
RESULTS
Table 1 shows a summary of data obtained in the bicarbonate-loaded dogs. During control and bicarbonate loading, GFR was significantly lower in the experimental kidney than in the control kidney. Volume expansion led to a significant increase in GFR in the EK but not in the CK; after volume expansion there was no significant difference in GFR of the two kidneys. RPF was lower in the EK than in the CK, but this difference was significant only during bicarbonate loading. After volume expansion, RPF did not change significantly in either the CK or the EK. There was no significant difference in filtration fraction between the CK and the EK. During control, fractional sodium excretion, although slightly greater in the EK was not significantly different from the CK (3.3 t 1.20 vs. 1.9 t 0.50). Figure 1 plots bicarbonate reabsorption against plasma bicarbonate concentration during bicarbonate loading and volume expansion. As can be seen during bicarbonate loading, bicarbonate reabsorption is significantly higher in the EK than in the CK (2.59 vs. 2.28 meq/lOO ml of GFR, P < 0.01; EKy = 3.05 - 0.01~ and CKy = 1.31 + 0.03x.) The 95% confidence limits do not overlap. Figure 2 plots bicarbonate reabsorption against fractional chloride excretion. During bicarbonate loading, bicarbonate reabsorption for any given fractional chloride excretion was higher in the EK than in the CK. Volume expansion (Figs. 1 and 2) led to a significant depression of bicarbonate reabsorption in both kidneys. After volume expansion, there was no significant difference in bicarbonate reabsorption between the EK and obstruction
Plasma HCO,
HCO, Reabsorption
meqlliter
meqlliter GFR
(C,,/GFR) x 100
(C,,,/GFR) x 100
%
UKV peqlmin
UPH per 100 ml GFR
upco* mmHg
19.4 I!z 0.80 P -=I 0.001 25.9 * 0.70 P < 0.001 18.9 + 1.20
3.4 It 1.40 NS 4.9 2 1.00 P < 0.001 22.9 + 2.10
7.9 ?I 2.00 P < 0.01 21.0 + 4.00 P < 0.001 39.6 IL 4.60
64.2 + 9.40 P < 0.01 103.5 + 11.50 NS 115.6 + 9.30
7.14 + 0.06 P < 0.001 7.80 + 0.03 P < 0.01 7.69 2 0.03
38.3 2 2.00 NS 42.3 +- 2.10 P < 0.05 39.2 + 1.50
19.8 + 0.80 P < 0.01 22.8 +- 0.60 P < 0.001 17.7 + 1.00
2.1 -t 0.79 P < 0.01 6.1 rf 1.50 P < 0.001 23.8 2 1.70
20.9 + 4.10 P < 0.001 42.3 -t 5.30 P < 0.05 56.4 -t 1.90
78.2 + 6.60 P < 0.001 162.5 2 10.00 NS 175.9 2 11.20
6.84 k 0.10 P -=I 0.001 7.80 + 0.03 P < 0.01 7.69 + 0.02
66.0 r+ 6.60 NS 67.8 + 6.20 P < 0.01 45.7 + 2.30
periods NS P < 0.01 NS
NS NS NS
P < 0.01 P < 0.01 P < 0.01
NS P < 0.001 P < 0.001
P < 0.05 NS NS
P < 0.001 P < 0.001 P < 0.05
and the two volume-expanded NS NS NS loading
ARRUDA,
Renal plasma flow (RPF) in group I was estimated by measuring the clearance of PAH. Total renal blood flow (TRBF) in group 111 was measured as previously described (1); the methods of sectioning the kidneys and calculating distribution of renal blood flow were identical to those reported by Bay et al. (3). Data are presented as mean plus or minus standard error of the mean.
ureteral
20.2 k 0.80 P < 0.001 32.7 rt 0.43 NS 32.9 2 0.43
KOZLOV,
VE, volume-expanded
period.
Downloaded from www.physiology.org/journal/ajplegacy by ${individualUser.givenNames} ${individualUser.surname} (130.070.008.131) on October 3, 2018. Copyright © 1976 American Physiological Society. All rights reserved.
H+
SECRETION
AFTER
URETERAL
Bicorb
Loading
Vol Expansion 0 Experimental Kidney o Control Kidney 0
3.0 .
1
A
0 l
2.6
0
0
0
00.
0
p
