Renal tubular spontaneously
reabsorption hypertensive
in rats
WILLIAM J. ARENDSHORST AND WILLIAM H. BEIERWALTES Department of Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514
ARENDSHORST,~ILLIAM J., AND WILLIAM H. BEIERWALTES. Renal tubular reabsorption in spontaneously hypertensive rats. Am. J. Physiol. 237(l): F38-F47, 1979 or Am. J. Physiol.: Renal Fluid Electrolyte Physiol. 6( 1): F38-F47,1979.-We characterized renal tubular reabsorption before and during acute expansion in anesthetized 12-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although mean arterial pressure was higher in euvolemic, nondiuretic SHR than in WKY, 158 vs. 114 mmHg, kidney and nephron glomerular filtration rate (GFR) as well as fluid reabsorption by the proximal convoluted tubule, loop of Henle, and distal convoluted tubule-collecting duct were similar. In euvolemic SHR with aortic constriction (SHR-AC), an acute decrease in renal perfusion pressure to 114 mmHg reduced sodium and water excretion. Kidney and nephron GFR and fluid reabsorption by segments along the nephron resembled values for SHR and WKY. Infusion of isotonic saline (3 100 g body wt-’ h-l) produced similar increases in fractional sodium and water excretion by SHR and WKY, whereas SHR-AC exhibited a blunted natriuresis and diuresis. During expansion, fluid reabsorption by the nephron segments did not differ appreciably among the three groups. The effect(s) of perfusion pressure on reabsorption by superficial nephrons may be covert and was not unmasked, or may be manifested preferentially by deeper nephrons. We conclude that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water. ml
l
l
sodium excretion; glomerular filtration rate; proximal tubule; loop of Henle; extracellular fluid volume; capillary pressure; arterial pressure; genetic hypertension ROLE OF THE KIDNEYS in the pathogenesis and maintenance of hypertension remains poorly understood despite intensive investigation. In most earlier studies of the renal involvement in experimental models, function of the kidney(s) was compromised by one or more interventions to produce a chronically elevated arterial pressure in previously normotensive animals. Only recently have investigations been conducted in the setting of genetic hypertension, in which experimental manipulations are not required to initiate the hypertension. In this regard, an animal strain characterized by spontaneous hypertension of genetic origin is considered to be a valuable model in which to investigate the mechanisms involved in the pathogenesis and maintenance of essential hypertension in man. Bianchi and associates (11) have presented evidence suggesting that a primary abnormality in renal function THE
F38
may initiate the hypertension in genetically hypertensive rats of the Milan strain. They postulated that hypertension may be caused by excessive retention of salt and water due to a lower glomerular filtration rate or enhanced proximal tubular reabsorption for a given renal perfusion pressure. Other laboratories have studied whole kidney function in spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain, especially the natriuresis and diuresis which follow acute expansion of extracellular fluid volume. The results conflict. After intravenous administration of a salt load, renal excretion of sodium and water by anesthetized SHR was less than (17, 31), equal to (25, 31), or greater than (16, 25) that of normotensive rats. Recent micropuncture evidence argues for and against abnormal fluid reabsorption by specific nephron segments in SHR during nondiuretic conditions as well as following administration of an acute saline load (16, 31). In the present study we report clearance and micropuncture observations in anesthetized 12-wk-old SHR with established hypertension and in normotensive Wistar-Kyoto rats (WKY). After base-line reabsorption during a euvolemic nondiuretic period was characterized, the rats were volume expanded to determine the renal and nephron responses to an acute salt load. To further test the hypothesis that kidneys of hypertensive rats require a higher arterial pressure than kidneys of normotensive rats to excrete a given load of salt and water, renal perfusion pressure was acutely reduced to within the normotensive range in another group of SHR, and similar measurements were made during euvolemic and volume expansion periods. METHODS
Observations are reported on 28 male SHR (217 t 30 (SD) g body wt; 12 t 1 wk) and 13 male WKY (218 t 31 g body wt; 11 t 2 wk) of the Okamoto-Aoki strain (26, 27). The SHR were bred locally, brother-sister, from an original stock of SHR of F 36-38generations, obtained from Dr. Carl Hansen at the National Institutes of Health. Most of the WKY studied were bred locally; some were purchased from Charles River Breeding Laboratories (Wilmington, MA). Renal function and tubular reabsorption were similar overall, regardless of the source. The rats, deprived of food overnight but allowed free access to water prior to the experiment, were anesthetized by.
0363-6127/79/0000-0000$01.25
Copyright
0 1979 the American
Physiological
Society
Downloaded from www.physiology.org/journal/ajprenal by ${individualUser.givenNames} ${individualUser.surname} (129.081.226.078) on January 10, 2019.
RENAL
TUBULAR
REABSORPTION
IN
GENETIC
HYPERTENSION
an intraperitoneal injection of sodium pentobarbital (50 mg/kg body wt) and placed on a heating table that maintained body temperature at 3’7-38OC. Immediately after the induction of anesthesia, femoral arterial blood was sampled for an initial or presurgical determination of hematocrit and plasma protein concentration. The left kidney was exposed through an abdominal incision for micropuncture as previously described (3-5). The left ureter was catheterized with PE-10 polyethylene tubing; PE-50 tubing was used in a few cases and similar results were obtained. Femoral arterial pressure was monitored with a Statham P23Db pressure transducer connected to a Hewlett-Packard recorder. Our previous experience with normotensive rats, as well as the experience of others (1, 21, 24), and preliminary studies in SHR and WKY suggested that protein is lost progressively from the vasculature during an experiment. We have observed that hematocrit increases and plasma protein concentration decreases during and following the surgical preparation required for micropuncture. The following protocol was employed to maintain these indices of vascular fluid volume stable at the baseline values obtained before surgery and thus compensate for a loss of plasma protein and fluid (9). Heparinized plasma from donor rats was infused intravenously to 1.25 ml/100 g body wt during surgery and maintained at 10 ,ul/min for the duration of an experiment. Similar results were obtained for both SHR and WKY receiving plasma from either group. Saline (0.85% NaCl) containing [3H]inulin (ICN, Irvine, CA), 85 ,&ie 100 g body wt-’ h-‘, and para-aminohippurate (PAH) (Eastman Kodak, Rochester, NY), 3-4 mg 100 g body wt-l. h-‘, was infused into a jugular vein at a rate of 10 @min during a nondiuretic period. Micropuncture and clearance measurements began after a l-h stabilization period. Urine was collected for 60 min and femoral arterial blood was sampled at the beginning and end of each clearance period. Hematocrit was measured in heparinized capillary tubes. During the second phase of each experiment, isotonic saline was administered intravenously to 3 ml/100 g body wt over approximately 30 min, after which the rate was 3 ml0 100 g body wt-’ . h-l. Micropuncture and clearance measurements were resumed after a 30.min equilibration period. At the end of the 60-min experimental period, blood was sampled from the left renal vein for determination of PAH extraction. In another similarly prepared group of SHR, we evaluated the influence of reduced renal perfusion pressure on renal and nephron function. A ligature encircling the abdominal aorta above the renal arteries was constricted to maintain femoral arterial pressure at approximately 115 mmHg, the average pressure of WKY, for the duration of an experiment. After the nondiuretic period these SHR with aortic constriction (SHR-AC) were given an isotonic saline load as described above. Tubular fluid from three to six separate late proximal and early distal convolutions was collected during each period of an experiment with sharpened, siliconized, glass pipettes having external tip diameters of 7-14 pm. The tubular fluid collection and measurement procedures have been described previously (4). The last superficial l
l
F39 coils of proximal convoluted tubules were localized with the aid of intravenous injections of 0.05 ml of 5% buffered solution of FD&C green dye (Keystone Aniline and Chemical Co., Chicago). “Late” proximal convolutions were also identified by intraluminal injections of an oil droplet or green dye (4). Similar results were obtained with both methods of localization. “Early” distal convolutions were identified as those in which the dye injected intravenously first appeared on the kidney surface after its transit through the loop .of Henle. Hydrostatic pressure in random surface proximal and distal convolutions and postglomerular vessels was measured with a continuously recording electronic servo-nulling apparatus and sharpened glass pipettes (3-7 pm OD) filled with 2 M NaCl (3-5). Inasmuch as glomeruli were not accessible for direct micropuncture, glomerular capillary pressure was estimated from the sum of stop-flow hydrostatic pressure, measured in the earliest accessible coil of a proximal tubule as previously described (3-5), and colloid osmotic pressure of systemic plasma. The radioactivity in tubular fluid, urine, and plasma samples was measured using a liquid scintillation spectrometer. The concentration of PAH in urine and plasma samples was determined by an adaptation of Bratton and Marshall’s method (12). A flame-emission spectrophotometer was used to measure urinary sodium concentration. We determined plasma protein concentration by an adaptation of the Lowry technique (14) using rateplasma total protein standards. Colloid osmotic pressure was calculated according to the Landis-Pappenheimer equation (20)) which we have validated for rat plasma (5). Glomerular filtration rate (GFR) was measured by the clearance of inulin, and renal plasma flow (RPF) was determined from the clearance and extraction of PAH. The filtration fraction (FF) was calculated as the ratio of GFR/RPF. Renal blood flow (RBF) was determined from RPF/( 1 - hematocrit), and renal vascular resistance (RVR) was calculated as arterial pressure/RBF. Fractional sodium excretion was calculated assuming a plasma sodium concentration of 140 meq/liter. Clearance data are reported for the left kidneys which were studied using micropuncture techniques. Single nephron glomerular filtration rate (SNGFR) was calculated as the fluid-to-plasma (F/P) inulin concentration ratio times tubular fluid flow rate (measured in nanoliters per minute). Delivery of tubular fluid to the early distal convolution was the measured tubular fluid flow rate (VED) at this site. Delivery of tubular fluid from the late proximal convolution (VL,) was determined by dividing SNGFR as measured from distal collections by the F/P inulin ratio at the proximal puncture site. Fluid delivery from a nephron at the terminal end of the collecting duct (Vcu) was estimated as distal SNGFR/ (U/P)I,. Absolute reabsorption of filtrate by the proximal convoluted tubule was calculated from distal SNGFR VLp, and absolute reabsorption between late proximal and early distal convolutions was determined as VLp VEn and used as an estimate of reabsorption by the loop of Henle. For this purpose, the loop of Henle is defined as the portion of the nephron between the last proximal coil on the kidney surface and the earliest distal convolution accessible to micropuncture. Absolute fluid reab-
Downloaded from www.physiology.org/journal/ajprenal by ${individualUser.givenNames} ${individualUser.surname} (129.081.226.078) on January 10, 2019.
F40
W. J. ARENDSHORST
sorption by nephron segments between the early distal puncture site and the pelvis, i.e., distal convoluted tubule and collecting duct, was calculated as &I-J - VCD, assuming homogeneity of nephron function. Fractional reabsorption by the proximal convoluted tubule was determined as [l - (P/F)*,3 x 100. Fractional reabsorption by the loop of HenIe was estimated as (absolute reabsorption/&) x 100 and by the distal convoluted tubule and collecting duct as (absolute reabsorption/V& x 100. Student’s t test for paired or unpaired variates, as appropriate, was performed for analysis of significance. Results considered statistically significant had P values of less than 0.05. The values given were calculated from the means during each observation period in an individual animal. RESULTS
Values for hematocrit and plasma protein concentration were almost identical before surgery and during the nondiuretic observation period in each group (Table 1)) which indicates that the infusion of donor plasma was effective in maintaining these indices of plasma volume stable. Both SHR groups had a higher initial hematocrit than WKY, but plasma protein concentration was similar in the three groups. Mean arterial pressure was higher in 12.wk-old euvolemic SHR than in WKY, averaging 158 and 114 mmHg, respectively. Clearance data obtained during the nondiuretic period are summarized in Table 2. Mean GFR was similar in SHR and WKY, but RPF was less and FF was greater in SHR. Although renal perfusion pressure was different, urine flow and sodium excretion were the same in both groups, as was fractional excretion (Fig. 1). In nondiuretic SHR-AC, femoral arterial pressure averaged 1. Hematocrit andplasmaprotein before surgery and during nondiuretic volume expansion observation periods TABLE
WKY
(n = 13)
concentration and
SHR (n = 14)
Hematocrit,
SHR-AC
(n = 14)
ml/l 00 ml
Presurgery
45 *2
to.001 *
49 A3
50 +3
tO.oolj-
Nondiuretic
44 *3
reabsorption hypertensive
in rats
WILLIAM J. ARENDSHORST AND WILLIAM H. BEIERWALTES Department of Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514
ARENDSHORST,~ILLIAM J., AND WILLIAM H. BEIERWALTES. Renal tubular reabsorption in spontaneously hypertensive rats. Am. J. Physiol. 237(l): F38-F47, 1979 or Am. J. Physiol.: Renal Fluid Electrolyte Physiol. 6( 1): F38-F47,1979.-We characterized renal tubular reabsorption before and during acute expansion in anesthetized 12-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although mean arterial pressure was higher in euvolemic, nondiuretic SHR than in WKY, 158 vs. 114 mmHg, kidney and nephron glomerular filtration rate (GFR) as well as fluid reabsorption by the proximal convoluted tubule, loop of Henle, and distal convoluted tubule-collecting duct were similar. In euvolemic SHR with aortic constriction (SHR-AC), an acute decrease in renal perfusion pressure to 114 mmHg reduced sodium and water excretion. Kidney and nephron GFR and fluid reabsorption by segments along the nephron resembled values for SHR and WKY. Infusion of isotonic saline (3 100 g body wt-’ h-l) produced similar increases in fractional sodium and water excretion by SHR and WKY, whereas SHR-AC exhibited a blunted natriuresis and diuresis. During expansion, fluid reabsorption by the nephron segments did not differ appreciably among the three groups. The effect(s) of perfusion pressure on reabsorption by superficial nephrons may be covert and was not unmasked, or may be manifested preferentially by deeper nephrons. We conclude that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water. ml
l
l
sodium excretion; glomerular filtration rate; proximal tubule; loop of Henle; extracellular fluid volume; capillary pressure; arterial pressure; genetic hypertension ROLE OF THE KIDNEYS in the pathogenesis and maintenance of hypertension remains poorly understood despite intensive investigation. In most earlier studies of the renal involvement in experimental models, function of the kidney(s) was compromised by one or more interventions to produce a chronically elevated arterial pressure in previously normotensive animals. Only recently have investigations been conducted in the setting of genetic hypertension, in which experimental manipulations are not required to initiate the hypertension. In this regard, an animal strain characterized by spontaneous hypertension of genetic origin is considered to be a valuable model in which to investigate the mechanisms involved in the pathogenesis and maintenance of essential hypertension in man. Bianchi and associates (11) have presented evidence suggesting that a primary abnormality in renal function THE
F38
may initiate the hypertension in genetically hypertensive rats of the Milan strain. They postulated that hypertension may be caused by excessive retention of salt and water due to a lower glomerular filtration rate or enhanced proximal tubular reabsorption for a given renal perfusion pressure. Other laboratories have studied whole kidney function in spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain, especially the natriuresis and diuresis which follow acute expansion of extracellular fluid volume. The results conflict. After intravenous administration of a salt load, renal excretion of sodium and water by anesthetized SHR was less than (17, 31), equal to (25, 31), or greater than (16, 25) that of normotensive rats. Recent micropuncture evidence argues for and against abnormal fluid reabsorption by specific nephron segments in SHR during nondiuretic conditions as well as following administration of an acute saline load (16, 31). In the present study we report clearance and micropuncture observations in anesthetized 12-wk-old SHR with established hypertension and in normotensive Wistar-Kyoto rats (WKY). After base-line reabsorption during a euvolemic nondiuretic period was characterized, the rats were volume expanded to determine the renal and nephron responses to an acute salt load. To further test the hypothesis that kidneys of hypertensive rats require a higher arterial pressure than kidneys of normotensive rats to excrete a given load of salt and water, renal perfusion pressure was acutely reduced to within the normotensive range in another group of SHR, and similar measurements were made during euvolemic and volume expansion periods. METHODS
Observations are reported on 28 male SHR (217 t 30 (SD) g body wt; 12 t 1 wk) and 13 male WKY (218 t 31 g body wt; 11 t 2 wk) of the Okamoto-Aoki strain (26, 27). The SHR were bred locally, brother-sister, from an original stock of SHR of F 36-38generations, obtained from Dr. Carl Hansen at the National Institutes of Health. Most of the WKY studied were bred locally; some were purchased from Charles River Breeding Laboratories (Wilmington, MA). Renal function and tubular reabsorption were similar overall, regardless of the source. The rats, deprived of food overnight but allowed free access to water prior to the experiment, were anesthetized by.
0363-6127/79/0000-0000$01.25
Copyright
0 1979 the American
Physiological
Society
Downloaded from www.physiology.org/journal/ajprenal by ${individualUser.givenNames} ${individualUser.surname} (129.081.226.078) on January 10, 2019.
RENAL
TUBULAR
REABSORPTION
IN
GENETIC
HYPERTENSION
an intraperitoneal injection of sodium pentobarbital (50 mg/kg body wt) and placed on a heating table that maintained body temperature at 3’7-38OC. Immediately after the induction of anesthesia, femoral arterial blood was sampled for an initial or presurgical determination of hematocrit and plasma protein concentration. The left kidney was exposed through an abdominal incision for micropuncture as previously described (3-5). The left ureter was catheterized with PE-10 polyethylene tubing; PE-50 tubing was used in a few cases and similar results were obtained. Femoral arterial pressure was monitored with a Statham P23Db pressure transducer connected to a Hewlett-Packard recorder. Our previous experience with normotensive rats, as well as the experience of others (1, 21, 24), and preliminary studies in SHR and WKY suggested that protein is lost progressively from the vasculature during an experiment. We have observed that hematocrit increases and plasma protein concentration decreases during and following the surgical preparation required for micropuncture. The following protocol was employed to maintain these indices of vascular fluid volume stable at the baseline values obtained before surgery and thus compensate for a loss of plasma protein and fluid (9). Heparinized plasma from donor rats was infused intravenously to 1.25 ml/100 g body wt during surgery and maintained at 10 ,ul/min for the duration of an experiment. Similar results were obtained for both SHR and WKY receiving plasma from either group. Saline (0.85% NaCl) containing [3H]inulin (ICN, Irvine, CA), 85 ,&ie 100 g body wt-’ h-‘, and para-aminohippurate (PAH) (Eastman Kodak, Rochester, NY), 3-4 mg 100 g body wt-l. h-‘, was infused into a jugular vein at a rate of 10 @min during a nondiuretic period. Micropuncture and clearance measurements began after a l-h stabilization period. Urine was collected for 60 min and femoral arterial blood was sampled at the beginning and end of each clearance period. Hematocrit was measured in heparinized capillary tubes. During the second phase of each experiment, isotonic saline was administered intravenously to 3 ml/100 g body wt over approximately 30 min, after which the rate was 3 ml0 100 g body wt-’ . h-l. Micropuncture and clearance measurements were resumed after a 30.min equilibration period. At the end of the 60-min experimental period, blood was sampled from the left renal vein for determination of PAH extraction. In another similarly prepared group of SHR, we evaluated the influence of reduced renal perfusion pressure on renal and nephron function. A ligature encircling the abdominal aorta above the renal arteries was constricted to maintain femoral arterial pressure at approximately 115 mmHg, the average pressure of WKY, for the duration of an experiment. After the nondiuretic period these SHR with aortic constriction (SHR-AC) were given an isotonic saline load as described above. Tubular fluid from three to six separate late proximal and early distal convolutions was collected during each period of an experiment with sharpened, siliconized, glass pipettes having external tip diameters of 7-14 pm. The tubular fluid collection and measurement procedures have been described previously (4). The last superficial l
l
F39 coils of proximal convoluted tubules were localized with the aid of intravenous injections of 0.05 ml of 5% buffered solution of FD&C green dye (Keystone Aniline and Chemical Co., Chicago). “Late” proximal convolutions were also identified by intraluminal injections of an oil droplet or green dye (4). Similar results were obtained with both methods of localization. “Early” distal convolutions were identified as those in which the dye injected intravenously first appeared on the kidney surface after its transit through the loop .of Henle. Hydrostatic pressure in random surface proximal and distal convolutions and postglomerular vessels was measured with a continuously recording electronic servo-nulling apparatus and sharpened glass pipettes (3-7 pm OD) filled with 2 M NaCl (3-5). Inasmuch as glomeruli were not accessible for direct micropuncture, glomerular capillary pressure was estimated from the sum of stop-flow hydrostatic pressure, measured in the earliest accessible coil of a proximal tubule as previously described (3-5), and colloid osmotic pressure of systemic plasma. The radioactivity in tubular fluid, urine, and plasma samples was measured using a liquid scintillation spectrometer. The concentration of PAH in urine and plasma samples was determined by an adaptation of Bratton and Marshall’s method (12). A flame-emission spectrophotometer was used to measure urinary sodium concentration. We determined plasma protein concentration by an adaptation of the Lowry technique (14) using rateplasma total protein standards. Colloid osmotic pressure was calculated according to the Landis-Pappenheimer equation (20)) which we have validated for rat plasma (5). Glomerular filtration rate (GFR) was measured by the clearance of inulin, and renal plasma flow (RPF) was determined from the clearance and extraction of PAH. The filtration fraction (FF) was calculated as the ratio of GFR/RPF. Renal blood flow (RBF) was determined from RPF/( 1 - hematocrit), and renal vascular resistance (RVR) was calculated as arterial pressure/RBF. Fractional sodium excretion was calculated assuming a plasma sodium concentration of 140 meq/liter. Clearance data are reported for the left kidneys which were studied using micropuncture techniques. Single nephron glomerular filtration rate (SNGFR) was calculated as the fluid-to-plasma (F/P) inulin concentration ratio times tubular fluid flow rate (measured in nanoliters per minute). Delivery of tubular fluid to the early distal convolution was the measured tubular fluid flow rate (VED) at this site. Delivery of tubular fluid from the late proximal convolution (VL,) was determined by dividing SNGFR as measured from distal collections by the F/P inulin ratio at the proximal puncture site. Fluid delivery from a nephron at the terminal end of the collecting duct (Vcu) was estimated as distal SNGFR/ (U/P)I,. Absolute reabsorption of filtrate by the proximal convoluted tubule was calculated from distal SNGFR VLp, and absolute reabsorption between late proximal and early distal convolutions was determined as VLp VEn and used as an estimate of reabsorption by the loop of Henle. For this purpose, the loop of Henle is defined as the portion of the nephron between the last proximal coil on the kidney surface and the earliest distal convolution accessible to micropuncture. Absolute fluid reab-
Downloaded from www.physiology.org/journal/ajprenal by ${individualUser.givenNames} ${individualUser.surname} (129.081.226.078) on January 10, 2019.
F40
W. J. ARENDSHORST
sorption by nephron segments between the early distal puncture site and the pelvis, i.e., distal convoluted tubule and collecting duct, was calculated as &I-J - VCD, assuming homogeneity of nephron function. Fractional reabsorption by the proximal convoluted tubule was determined as [l - (P/F)*,3 x 100. Fractional reabsorption by the loop of HenIe was estimated as (absolute reabsorption/&) x 100 and by the distal convoluted tubule and collecting duct as (absolute reabsorption/V& x 100. Student’s t test for paired or unpaired variates, as appropriate, was performed for analysis of significance. Results considered statistically significant had P values of less than 0.05. The values given were calculated from the means during each observation period in an individual animal. RESULTS
Values for hematocrit and plasma protein concentration were almost identical before surgery and during the nondiuretic observation period in each group (Table 1)) which indicates that the infusion of donor plasma was effective in maintaining these indices of plasma volume stable. Both SHR groups had a higher initial hematocrit than WKY, but plasma protein concentration was similar in the three groups. Mean arterial pressure was higher in 12.wk-old euvolemic SHR than in WKY, averaging 158 and 114 mmHg, respectively. Clearance data obtained during the nondiuretic period are summarized in Table 2. Mean GFR was similar in SHR and WKY, but RPF was less and FF was greater in SHR. Although renal perfusion pressure was different, urine flow and sodium excretion were the same in both groups, as was fractional excretion (Fig. 1). In nondiuretic SHR-AC, femoral arterial pressure averaged 1. Hematocrit andplasmaprotein before surgery and during nondiuretic volume expansion observation periods TABLE
WKY
(n = 13)
concentration and
SHR (n = 14)
Hematocrit,
SHR-AC
(n = 14)
ml/l 00 ml
Presurgery
45 *2
to.001 *
49 A3
50 +3
tO.oolj-
Nondiuretic
44 *3
