0021-972X/9l/7206-1200$03.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1991 by The Endocrine Society
Vol. 72, No. 6 Printed in U.S.A.
Lack of Enhanced Responsiveness of Plasma 18Hydroxycorticosterone and Aldosterone to Adrenocorticotropin as well as to Angiotensin-II during Moderate Sodium Depletion in Type II Diabetic Subjects with Normoreninemia TOSHIKAZU KIGOSHI*, RYOJI IWASAKI, MIHOKO KANEKO, SHIGERU NAKANO, SADAHIDE AZUKIZAWA, KENZO UCHIDA, AND SHINPEI MORIMOTO Division of Endocrinology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa 920-02, Japan
ABSTRACT. Responses of plasma aldosterone (PA) and its precursor steroids to aACTH-(l-24) (85.2 nmol, iv) injection and graded angiotensin-II (All) infusions (3.90 and 7.80 pmol/ kg-min for 30 min at each dose) on both 170 and 100 mmol sodium intakes were assessed in 25 type II diabetic subjects with normoreninemia and 11 age-matched normal subjects. The diabetic subjects and the normal subjects did not differ in mean blood pressure, serum electrolytes, and creatinine clearance, except for an increase in fasting plasma glucose (P < 0.001) in the diabetic subjects. A 100-mmol sodium intake for 4 days produced an increase in basal plasma renin activity (P < 0.01), plasma 18-hydroxycorticosterone (18-OHB; P < 0.05), and PA (P < 0.05), and a decrease in urinary sodium excretion (P < 0.001) in the two groups. These parameters were similar in the two groups. ACTH injection produced significant increases in
D
IABETES mellitus is frequently associated with a blunted responsiveness of plasma aldosterone (PA) to various stimuli, including postural change (1-3), furosemide administration (3), and angiotensin-II (All) (4, 5). The blunted aldosterone responsiveness to these stimuli has been partly explained by concomitant renin deficiency (4-8). A primary adrenal abnormality also may contribute to the blunted responsiveness of PA to All in some diabetic patients without hyporeninemia (911). The response of PA to ACTH in diabetes mellitus, however, is still controversial. The PA response to ACTH in nonazotemic diabetes mellitus has been reported to be both altered (2, 4, 5, 12) and unaltered (3, 10-13). Although this discrepancy may be partly due to the difference in the patient populations studied, there is another possible explanation. It is well known that the response Received June 6,1990. * Address all correspondence and requests for reprints to: Dr. T. Kigoshi, Division of Endocrinology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa 920-02, Japan.
plasma cortisol, plasma corticosterone, plasma 18-OHB, and PA (P < 0.005 or P < 0.001), and graded All infusions produced significant increases in plasma 18-OHB and PA (P < 0.05 or P < 0.01) during both 170- and 100-mmol sodium intakes in the two groups. In the diabetic subjects, however, the responses of plasma 18-OHB and PA to both ACTH injection and graded All infusions on a 100-mmol, but not on a 170-mmol, sodium intake were subnormal (P < 0.05 or P < 0.01) and were similar to those on a 170-mmol sodium intake. These results indicate a lack of enhanced responsiveness of plasma 18-OHB and PA to both ACTH and All during moderate sodium restriction in nonazotemic type II diabetic subjects with normoreninemia. It appears that these subjects have selective unresponsiveness of adrenal zona glomerulosa to sodium depletion per se, but not to ACTH or All. (J Clin Endocrinol Metab 72: 1200-1205,1991)
of the adrenal zona glomerulosa to ACTH as well as that to All are critically dependent on sodium intake or sodium balance and are enhanced by sodium restriction (14). Since exchangeable sodium has been shown to be increased in nonazotemic diabetes mellitus (1, 3), the abnormal body sodium balance may modify the responsiveness of PA to both ACTH and All in nonazotemic diabetes mellitus. To assess in detail the response of PA to both ACTH and All in diabetes mellitus, we measured plasma levels of aldosterone and its precursor steroids in response to both ACTH injection and graded All infusions during both unrestricted and restricted sodium intakes in nonazotemic diabetic subjects with normoreninemia.
Subjects and Methods Twenty-five type II diabetic subjects (17 men and 8 women) with normoreninemia and 11 age-matched normal subjects (6 men and 5 women) were studied at the Kanazawa Medical University Hospital after informed consent was obtained from
1200
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ALDOSTERONE RESPONSIVENESS IN DIABETES MELLITUS each participant. The age of the diabetic subjects ranged from 26-66 yr (mean, 53 ± 2 yr). The 25 diabetic subjects were selected as having normoreninemia by the following criteria: a PRA level greater than 0.50 ng/L • s and a PA level greater than 282.9 pmol/L after furosemide administration (80 mg, orally) plus upright posture (4 h) to avoid normoreninemic hypoaldosteronism (10). Normal subjects after the stimulation uniformly have PA levels greater than 282.9 pmol/L and PRA levels greater than 0.50 ng/L-s, as measured in our laboratory (15). Diabetes mellitus was established by standard laboratory methods; the known duration of diabetes ranged from 1-25 yr (mean, 6 ± 1 yr). On admission, 12 patients were treated with diet alone, 8 with diet and orally administered hypoglycemic agents, and 5 with diet and insulin. Diabetic retinopathy was found in 9, proteinuria (132.6 jumol/L). The normal subjects were in good health for their age and had no history of hypertension, heart disease, or renal disease. All of the diabetic subjects with normoreninemia and the normal subjects were placed on a 170-mmol sodium intake for a week and then a 100-mmol sodium intake for 5 days, although the diabetic patients with normoreninemia were eating a standard diabetic diet relative to height, weight, and age. Each subject was instructed to collect a 24-h urine specimen (from 0600-0600 h). ACTH injection was started between 0800-0900 h after overnight recumbency on both the seventh day of a 170-mmol sodium intake and the fifth day of a 100-mmol sodium intake. «ACTH-(l-24) (Cortrosyn, Organon, West Orange, NJ) was injected iv in a single dose of 85.2 nmol. A blood sample was obtained immediately before, and 30 and 60 min after the injection. Graded All infusions were also performed in the early morning after overnight recumbency on both the sixth day of a 170-mmol sodium intake and the sixth day of a 100-mmol sodium intake. All amide (Ciba-Geigy, Basel, Switzerland) was infused iv at rates of 3.90 and 7.80 pmol/kg-min for 30 min at each dose. Blood pressure was measured with a cuff sphygmomanometer at 2-min intervals during each dose of All. A blood sample was drawn at the end of the preinfusion period and just before the end of each All infusion period. All blood samples for assays of PRA and plasma corticosteroids were collected in tubes containing heparin sodium and immediately centrifuged at 4 C. The plasma was frozen at -20 C until assayed. PRA was measured by RIA, using kits from Dinabott Radioisotope Institute (Tokyo, Japan). Plasma cortisol and plasma corticosterone were measured by RIA, using their specific antisera purchased from Endocrine Sciencies (Tarzana, CA), and Teikoku Hormone Mfg. Co. (Kawasaki, Japan), respectively. Details of these methods have been reported previously (16). Plasma 18-hydroxycorticosterone (18-OHB) and PA were determined by RIA after the separation of these corticoids from cross-reacting steroids by means of high performance liquid chromatography, as described previously (17). Results are expressed as the mean ± SEM. Differences between the diabetic subjects with normoreninemia and the normal subjects were analyzed by Student's t test. Comparisons of the responses of plasma corticosteroids to ACTH injection or
1201
graded All infusions in the two groups were evaluated using repeated measures analysis of variance.
Results Clinical and biochemical data (Table 1) Diabetic subjects with normoreninemia and normal subjects did not differ in serum sodium, serum potassium, and creatinine clearance, except for an increase in fasting plasma glucose (P < 0.001) in the diabetic subjects. Although age and mean blood pressure tended to be higher in the diabetic subjects than in the normal subjects, differences in these parameters between the two groups were not significant. There were also no significant differences between the two groups in urine volume and urinary sodium and potassium excretion during the 4-h period of furosemide administration plus upright posture stimulation. Basal and stimulated levels of PRA, plasma cortisol, serum sodium, and serum potassium were similar in the two groups. Basal levels of PA were similar in the two groups, whereas the stimulated levels of PA were significantly lower (P < 0.01) in the diabetic TABLE 1. Clinical and biochemical data Normal subjects
Diabetic subjects with normoreninemia
n
Age (yr) Sex (M/F) Duration of diabetes (yr) Mean blood pressure (mm Hg) Fasting plasma glucose (mmol/L) Serum sodium (mmol/L) Serum potassium (mmol/L) Plasma cortisol (nmol/L) Basal After F plus U stimulation PRA (ng/L -s) Basal After F plus U stimulation PA (pmol/L) Basal After F plus U stimulation Urine volume (mL/4 h) Urinary sodium excretion (mmol/4 h) Urinary potassium excretion (mmol/4 h) Creatinine clearance (mL/s)
n
25
47 ± 3 6/5
53 ± 2 17/8 6±1 99 ± 5
87 ± 3 4.55 ± 0.06
7.27 ± 0.22°
141.9 ± 0.6 3.9 ± 0.1
140.9 ± 0.4 4.1 ± 0.1
383.5 ± 24.8 427.6 ± 27.6
438.7 ± 22.1 452.5 ± 24.8
0.28 ± 0.03 1.17 ± 0.19
0.33 ± 0.06 1.14 ± 0.14
183.1 ± 13.9 524.3 ± 27.7 1275 ± 155 160.5 ± 23.9
194.2 ± 19.4 402.2 ± 25.06 1120 ± 70 135.5 ± 18.9
26.0 ± 3.9
21.4 ± 1.0
1.63 ± 0.08
1.34 ± 0.07
Values are the mean ± SEM. F, Furosemide; U, upright posture. Urine volume and urinary sodium and potassium excretions are values during the 4-h period of F plus U stimulation. " P < 0.001 vs. corresponding value for normal subjects. b P < 0.01 vs. corresponding value for normal subjects.
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KIGOSHI ET AL.
1202
subjects with normoreninemia compared with levels in the normal subjects. Effect of a 100-mmol sodium intake on baseline measurements of metabolic and endocrine functions (Tables 2 and 3) A 100-mmol sodium intake for 4 days produced a significant increase in basal PRA (P < 0.01), plasma 18OHB (P < 0.05), and PA (P < 0.01) and a significant decrease in urinary sodium excretion (P < 0.001) in both the normal subjects and the diabetic subjects. There were, however, no significant differences between the two groups in serum sodium, serum potassium, PRA, plasma corticosterone, plasma cortisol, plasma 18-OHB, and PA during the 100-mmol sodium intake. The ratio of plasma 18-OHB to PA was similar in the two groups (data not shown). As shown in Table 3, 24-h urinary excretion of sodium, but not of potassium, gradually decreased (P < 0.01 or P < 0.001) during a 100-mmol sodium intake and reached almost a plateau on the fourth day of a 100-mmol sodium intake in both the diabetic subjects and the normal subjects. There were, however, no significant differences between the two groups in urinary excretion of sodium and potassium during a 100mmol sodium intake. Effect ofACTH injection on plasma corticosteroids on both 170- and 100-mmol sodium intakes (Figs. 1 and 2) Normal and diabetic subjects had similar pre-ACTH plasma corticosterone and plasma cortisol levels on both 170- and 100-mmol sodium intakes. ACTH injection produced similarly increases in plasma corticosterone
JCE & M • 1991 Vol 72 • No 6
and plasma cortisol 30 and 60 min later in the two groups on both 170- and 100-mmol sodium intakes (P < 0.005; Fig. 1). Pre-ACTH levels of plasma 18-OHB and PA on both 170- and 100-mmol sodium intakes were similar between the two groups. ACTH injection similarly produced increases in plasma 18-OHB and PA 30 and 60 min later in the two groups on the 170-mmol sodium intake (P < 0.001). ACTH injection also produced significant increases in plasma 18-OHB and PA 30 and 60 min later in the two groups on a 100-mmol sodium intake (P < 0.001). The responses of plasma 18-OHB and PA to ACTH injection on a 100-mmol sodium intake, however, were significantly lower (P < 0.01) in the diabetic subjects than those in the normal subjects. Effect of graded AH infusions on mean blood pressure, plasma 18-OHB, and PA on both 170- and 100-mmol sodium intakes (Fig. 3) The normal and diabetic subjects had similar pre-AII mean blood pressure, plasma 18-OHB, and PA levels on both 170- and 100-mmol sodium intakes. Graded All infusions similarly produced dose-related increases in mean blood pressure at doses of 3.90 and 7.80 pmol/kgmin in the two groups on both 170- and 100-mmol sodium intakes (P < 0.01). Graded All infusions similarly produced dose-related increases in plasma 18-OHB and PA at 3.90 and 7.80 pmol/kg-min doses in the two groups on the 170-mmol sodium intake (P < 0.05 or P < 0.01). Graded All infusions also produced dose-related increases in plasma 18-OHB and PA at doses of 3.90 and 7.80 pmol/kg-min in the two groups on the 100-mmol
TABLE 2. Effects of 170- and 100-mmol sodium intakes on baseline measurements of metabolic and endocrine functions in both 11 normal subjects and 25 diabetic subjects Diabetic subjects with
Normal subjects Sodium intake (mmol)
normoreninemia 170
BW loss (kg) Serum electrolytes (mmol/L) Serum sodium Serum potassium Urinary electrolytes (mmol/24 h) Sodium Potassium PRA(ng/L-s) Plasma cortisol (nmol/L) Plasma corticosterone (nmol/L) Plasma 18-OHB (pmol/L) Plasma aldosterone (pmol/L)
100
170
100
0.8 ± 0.1
0.8 ± 0.1
141.1 ± 0.5 4.1 ± 0.1
140.2 ± 0.6 4.1 ± 0.1
141.4 ± 0.4 4.2 ± 0.1
140.5 ± 0.4 4.2 ± 0.1
150.9 ± 29.3 ± 0.28 ± 350.4 ± 14.16 ± 544.1 ± 183.1 ±
94.5 ± 34.3 ± 0.61 ± 303.5 ± 14.45 ± 781.6 ± 310.7 ±
147.3 ± 5.4 34.1 ± 2.7 0.31 ± 0.06 331.1 ± 16.6 13.29 ± 0.61 486.1 ± 99.4 188.6 ± 13.9
71.7 ± 8.3° 35.9 ± 3.1 0.58 ± 0.03* 344.9 ± 16.6 13.87 ± 1.21 726.4 ± 88.4C 249.7 ± 19.4*
6.1 3.1 0.03 41.4 0.95 82.9 25.0
5.8° 2.8 0.066 24.8 1.44 77.3C 30.56
Values are the means ± SEM. Significance is expressed vs. corresponding value during a 170-mmol sodium intake. ° P < 0.001. 6 P
Vol. 72, No. 6 Printed in U.S.A.
Lack of Enhanced Responsiveness of Plasma 18Hydroxycorticosterone and Aldosterone to Adrenocorticotropin as well as to Angiotensin-II during Moderate Sodium Depletion in Type II Diabetic Subjects with Normoreninemia TOSHIKAZU KIGOSHI*, RYOJI IWASAKI, MIHOKO KANEKO, SHIGERU NAKANO, SADAHIDE AZUKIZAWA, KENZO UCHIDA, AND SHINPEI MORIMOTO Division of Endocrinology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa 920-02, Japan
ABSTRACT. Responses of plasma aldosterone (PA) and its precursor steroids to aACTH-(l-24) (85.2 nmol, iv) injection and graded angiotensin-II (All) infusions (3.90 and 7.80 pmol/ kg-min for 30 min at each dose) on both 170 and 100 mmol sodium intakes were assessed in 25 type II diabetic subjects with normoreninemia and 11 age-matched normal subjects. The diabetic subjects and the normal subjects did not differ in mean blood pressure, serum electrolytes, and creatinine clearance, except for an increase in fasting plasma glucose (P < 0.001) in the diabetic subjects. A 100-mmol sodium intake for 4 days produced an increase in basal plasma renin activity (P < 0.01), plasma 18-hydroxycorticosterone (18-OHB; P < 0.05), and PA (P < 0.05), and a decrease in urinary sodium excretion (P < 0.001) in the two groups. These parameters were similar in the two groups. ACTH injection produced significant increases in
D
IABETES mellitus is frequently associated with a blunted responsiveness of plasma aldosterone (PA) to various stimuli, including postural change (1-3), furosemide administration (3), and angiotensin-II (All) (4, 5). The blunted aldosterone responsiveness to these stimuli has been partly explained by concomitant renin deficiency (4-8). A primary adrenal abnormality also may contribute to the blunted responsiveness of PA to All in some diabetic patients without hyporeninemia (911). The response of PA to ACTH in diabetes mellitus, however, is still controversial. The PA response to ACTH in nonazotemic diabetes mellitus has been reported to be both altered (2, 4, 5, 12) and unaltered (3, 10-13). Although this discrepancy may be partly due to the difference in the patient populations studied, there is another possible explanation. It is well known that the response Received June 6,1990. * Address all correspondence and requests for reprints to: Dr. T. Kigoshi, Division of Endocrinology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa 920-02, Japan.
plasma cortisol, plasma corticosterone, plasma 18-OHB, and PA (P < 0.005 or P < 0.001), and graded All infusions produced significant increases in plasma 18-OHB and PA (P < 0.05 or P < 0.01) during both 170- and 100-mmol sodium intakes in the two groups. In the diabetic subjects, however, the responses of plasma 18-OHB and PA to both ACTH injection and graded All infusions on a 100-mmol, but not on a 170-mmol, sodium intake were subnormal (P < 0.05 or P < 0.01) and were similar to those on a 170-mmol sodium intake. These results indicate a lack of enhanced responsiveness of plasma 18-OHB and PA to both ACTH and All during moderate sodium restriction in nonazotemic type II diabetic subjects with normoreninemia. It appears that these subjects have selective unresponsiveness of adrenal zona glomerulosa to sodium depletion per se, but not to ACTH or All. (J Clin Endocrinol Metab 72: 1200-1205,1991)
of the adrenal zona glomerulosa to ACTH as well as that to All are critically dependent on sodium intake or sodium balance and are enhanced by sodium restriction (14). Since exchangeable sodium has been shown to be increased in nonazotemic diabetes mellitus (1, 3), the abnormal body sodium balance may modify the responsiveness of PA to both ACTH and All in nonazotemic diabetes mellitus. To assess in detail the response of PA to both ACTH and All in diabetes mellitus, we measured plasma levels of aldosterone and its precursor steroids in response to both ACTH injection and graded All infusions during both unrestricted and restricted sodium intakes in nonazotemic diabetic subjects with normoreninemia.
Subjects and Methods Twenty-five type II diabetic subjects (17 men and 8 women) with normoreninemia and 11 age-matched normal subjects (6 men and 5 women) were studied at the Kanazawa Medical University Hospital after informed consent was obtained from
1200
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 28 November 2015. at 10:43 For personal use only. No other uses without permission. . All rights reserved.
ALDOSTERONE RESPONSIVENESS IN DIABETES MELLITUS each participant. The age of the diabetic subjects ranged from 26-66 yr (mean, 53 ± 2 yr). The 25 diabetic subjects were selected as having normoreninemia by the following criteria: a PRA level greater than 0.50 ng/L • s and a PA level greater than 282.9 pmol/L after furosemide administration (80 mg, orally) plus upright posture (4 h) to avoid normoreninemic hypoaldosteronism (10). Normal subjects after the stimulation uniformly have PA levels greater than 282.9 pmol/L and PRA levels greater than 0.50 ng/L-s, as measured in our laboratory (15). Diabetes mellitus was established by standard laboratory methods; the known duration of diabetes ranged from 1-25 yr (mean, 6 ± 1 yr). On admission, 12 patients were treated with diet alone, 8 with diet and orally administered hypoglycemic agents, and 5 with diet and insulin. Diabetic retinopathy was found in 9, proteinuria (132.6 jumol/L). The normal subjects were in good health for their age and had no history of hypertension, heart disease, or renal disease. All of the diabetic subjects with normoreninemia and the normal subjects were placed on a 170-mmol sodium intake for a week and then a 100-mmol sodium intake for 5 days, although the diabetic patients with normoreninemia were eating a standard diabetic diet relative to height, weight, and age. Each subject was instructed to collect a 24-h urine specimen (from 0600-0600 h). ACTH injection was started between 0800-0900 h after overnight recumbency on both the seventh day of a 170-mmol sodium intake and the fifth day of a 100-mmol sodium intake. «ACTH-(l-24) (Cortrosyn, Organon, West Orange, NJ) was injected iv in a single dose of 85.2 nmol. A blood sample was obtained immediately before, and 30 and 60 min after the injection. Graded All infusions were also performed in the early morning after overnight recumbency on both the sixth day of a 170-mmol sodium intake and the sixth day of a 100-mmol sodium intake. All amide (Ciba-Geigy, Basel, Switzerland) was infused iv at rates of 3.90 and 7.80 pmol/kg-min for 30 min at each dose. Blood pressure was measured with a cuff sphygmomanometer at 2-min intervals during each dose of All. A blood sample was drawn at the end of the preinfusion period and just before the end of each All infusion period. All blood samples for assays of PRA and plasma corticosteroids were collected in tubes containing heparin sodium and immediately centrifuged at 4 C. The plasma was frozen at -20 C until assayed. PRA was measured by RIA, using kits from Dinabott Radioisotope Institute (Tokyo, Japan). Plasma cortisol and plasma corticosterone were measured by RIA, using their specific antisera purchased from Endocrine Sciencies (Tarzana, CA), and Teikoku Hormone Mfg. Co. (Kawasaki, Japan), respectively. Details of these methods have been reported previously (16). Plasma 18-hydroxycorticosterone (18-OHB) and PA were determined by RIA after the separation of these corticoids from cross-reacting steroids by means of high performance liquid chromatography, as described previously (17). Results are expressed as the mean ± SEM. Differences between the diabetic subjects with normoreninemia and the normal subjects were analyzed by Student's t test. Comparisons of the responses of plasma corticosteroids to ACTH injection or
1201
graded All infusions in the two groups were evaluated using repeated measures analysis of variance.
Results Clinical and biochemical data (Table 1) Diabetic subjects with normoreninemia and normal subjects did not differ in serum sodium, serum potassium, and creatinine clearance, except for an increase in fasting plasma glucose (P < 0.001) in the diabetic subjects. Although age and mean blood pressure tended to be higher in the diabetic subjects than in the normal subjects, differences in these parameters between the two groups were not significant. There were also no significant differences between the two groups in urine volume and urinary sodium and potassium excretion during the 4-h period of furosemide administration plus upright posture stimulation. Basal and stimulated levels of PRA, plasma cortisol, serum sodium, and serum potassium were similar in the two groups. Basal levels of PA were similar in the two groups, whereas the stimulated levels of PA were significantly lower (P < 0.01) in the diabetic TABLE 1. Clinical and biochemical data Normal subjects
Diabetic subjects with normoreninemia
n
Age (yr) Sex (M/F) Duration of diabetes (yr) Mean blood pressure (mm Hg) Fasting plasma glucose (mmol/L) Serum sodium (mmol/L) Serum potassium (mmol/L) Plasma cortisol (nmol/L) Basal After F plus U stimulation PRA (ng/L -s) Basal After F plus U stimulation PA (pmol/L) Basal After F plus U stimulation Urine volume (mL/4 h) Urinary sodium excretion (mmol/4 h) Urinary potassium excretion (mmol/4 h) Creatinine clearance (mL/s)
n
25
47 ± 3 6/5
53 ± 2 17/8 6±1 99 ± 5
87 ± 3 4.55 ± 0.06
7.27 ± 0.22°
141.9 ± 0.6 3.9 ± 0.1
140.9 ± 0.4 4.1 ± 0.1
383.5 ± 24.8 427.6 ± 27.6
438.7 ± 22.1 452.5 ± 24.8
0.28 ± 0.03 1.17 ± 0.19
0.33 ± 0.06 1.14 ± 0.14
183.1 ± 13.9 524.3 ± 27.7 1275 ± 155 160.5 ± 23.9
194.2 ± 19.4 402.2 ± 25.06 1120 ± 70 135.5 ± 18.9
26.0 ± 3.9
21.4 ± 1.0
1.63 ± 0.08
1.34 ± 0.07
Values are the mean ± SEM. F, Furosemide; U, upright posture. Urine volume and urinary sodium and potassium excretions are values during the 4-h period of F plus U stimulation. " P < 0.001 vs. corresponding value for normal subjects. b P < 0.01 vs. corresponding value for normal subjects.
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KIGOSHI ET AL.
1202
subjects with normoreninemia compared with levels in the normal subjects. Effect of a 100-mmol sodium intake on baseline measurements of metabolic and endocrine functions (Tables 2 and 3) A 100-mmol sodium intake for 4 days produced a significant increase in basal PRA (P < 0.01), plasma 18OHB (P < 0.05), and PA (P < 0.01) and a significant decrease in urinary sodium excretion (P < 0.001) in both the normal subjects and the diabetic subjects. There were, however, no significant differences between the two groups in serum sodium, serum potassium, PRA, plasma corticosterone, plasma cortisol, plasma 18-OHB, and PA during the 100-mmol sodium intake. The ratio of plasma 18-OHB to PA was similar in the two groups (data not shown). As shown in Table 3, 24-h urinary excretion of sodium, but not of potassium, gradually decreased (P < 0.01 or P < 0.001) during a 100-mmol sodium intake and reached almost a plateau on the fourth day of a 100-mmol sodium intake in both the diabetic subjects and the normal subjects. There were, however, no significant differences between the two groups in urinary excretion of sodium and potassium during a 100mmol sodium intake. Effect ofACTH injection on plasma corticosteroids on both 170- and 100-mmol sodium intakes (Figs. 1 and 2) Normal and diabetic subjects had similar pre-ACTH plasma corticosterone and plasma cortisol levels on both 170- and 100-mmol sodium intakes. ACTH injection produced similarly increases in plasma corticosterone
JCE & M • 1991 Vol 72 • No 6
and plasma cortisol 30 and 60 min later in the two groups on both 170- and 100-mmol sodium intakes (P < 0.005; Fig. 1). Pre-ACTH levels of plasma 18-OHB and PA on both 170- and 100-mmol sodium intakes were similar between the two groups. ACTH injection similarly produced increases in plasma 18-OHB and PA 30 and 60 min later in the two groups on the 170-mmol sodium intake (P < 0.001). ACTH injection also produced significant increases in plasma 18-OHB and PA 30 and 60 min later in the two groups on a 100-mmol sodium intake (P < 0.001). The responses of plasma 18-OHB and PA to ACTH injection on a 100-mmol sodium intake, however, were significantly lower (P < 0.01) in the diabetic subjects than those in the normal subjects. Effect of graded AH infusions on mean blood pressure, plasma 18-OHB, and PA on both 170- and 100-mmol sodium intakes (Fig. 3) The normal and diabetic subjects had similar pre-AII mean blood pressure, plasma 18-OHB, and PA levels on both 170- and 100-mmol sodium intakes. Graded All infusions similarly produced dose-related increases in mean blood pressure at doses of 3.90 and 7.80 pmol/kgmin in the two groups on both 170- and 100-mmol sodium intakes (P < 0.01). Graded All infusions similarly produced dose-related increases in plasma 18-OHB and PA at 3.90 and 7.80 pmol/kg-min doses in the two groups on the 170-mmol sodium intake (P < 0.05 or P < 0.01). Graded All infusions also produced dose-related increases in plasma 18-OHB and PA at doses of 3.90 and 7.80 pmol/kg-min in the two groups on the 100-mmol
TABLE 2. Effects of 170- and 100-mmol sodium intakes on baseline measurements of metabolic and endocrine functions in both 11 normal subjects and 25 diabetic subjects Diabetic subjects with
Normal subjects Sodium intake (mmol)
normoreninemia 170
BW loss (kg) Serum electrolytes (mmol/L) Serum sodium Serum potassium Urinary electrolytes (mmol/24 h) Sodium Potassium PRA(ng/L-s) Plasma cortisol (nmol/L) Plasma corticosterone (nmol/L) Plasma 18-OHB (pmol/L) Plasma aldosterone (pmol/L)
100
170
100
0.8 ± 0.1
0.8 ± 0.1
141.1 ± 0.5 4.1 ± 0.1
140.2 ± 0.6 4.1 ± 0.1
141.4 ± 0.4 4.2 ± 0.1
140.5 ± 0.4 4.2 ± 0.1
150.9 ± 29.3 ± 0.28 ± 350.4 ± 14.16 ± 544.1 ± 183.1 ±
94.5 ± 34.3 ± 0.61 ± 303.5 ± 14.45 ± 781.6 ± 310.7 ±
147.3 ± 5.4 34.1 ± 2.7 0.31 ± 0.06 331.1 ± 16.6 13.29 ± 0.61 486.1 ± 99.4 188.6 ± 13.9
71.7 ± 8.3° 35.9 ± 3.1 0.58 ± 0.03* 344.9 ± 16.6 13.87 ± 1.21 726.4 ± 88.4C 249.7 ± 19.4*
6.1 3.1 0.03 41.4 0.95 82.9 25.0
5.8° 2.8 0.066 24.8 1.44 77.3C 30.56
Values are the means ± SEM. Significance is expressed vs. corresponding value during a 170-mmol sodium intake. ° P < 0.001. 6 P
