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Calcium deprivation increases NaCl intake of fischer-344 rats
Physiology & Behavior, Vol. 49, pp. 113-115. ©PergamonPressplc, 1991.Printedin the U.S.A.
0031-9384/91 $3.00 + .00
Calcium Deprivation Increases NaC1 Intake of Fischer-344 Rats MICHAEL G. TORDOFF Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104-3308 Received 16 July 1990
TORDOFF, M. G. Calcium deprivation increases NaCl intake of Fischer-344 rats. PHYSIOL BEHAV 49(1) 113-115, 1991.Fischer-344 rats fed Ca2+-deficientdiet for 63 days increased intake of 0.3 M NaC1 solution from control levels of - 8 ml/day to >60 ml/day. During the same period, rats fed Na+-deficient diet drank ~11 ml/day. These results indicate that Fischer-344 rats, which generallyspurn NaCI, drink large amountsof it when Ca2+ deprived. Salt intake
Sodium
Strain differences
Calcium
FISCHER-344 rats differ from other strains used to study ingestive behavior in that they show little spontaneous intake of dilute NaC1 solution (6--8). Despite this, they respond to manipulations of the renin-angiotensin-aldosterone system such as adrenalectomy, dietary Na + restriction, or treatment with furosemide, deoxycorticosterone acetate, or angiotensin converting enzyme inhibitors [(7,8); reviews (9,10)]. Their response to these manipulations tends to be blunted relative to those of other strains, but it is still sufficient to satisfy Na + homeostasis. Recently, we found that a potent control of NaC1 intake is provided by some aspect of Ca2 + metabolism. Sprague DawIcy rats fed low-Ca2+ diets dramatically increase their voluntary NaC1 intake. These animals have normal plasma concentrations of Na +, aldosterone, and angiotensin I, and they retain Na + more efficiently than do controls (12). Given that neither the low NaC1 intake of Fischer-344 rats nor the high NaC1 intake of Ca2÷-deficient Sprague Dawley rats can easily be accounted for by dysfunctions of the renin-angiotensin-aldosteronesystem, it seemed worthwhile examining if Fischer-344 rats were sensitive to the effects of Ca2+ deprivation. METHOD The subjects were 28 male Fischer-344 rats, purchased from Charles River (Kingston, NY), weighing 67-88 g at the start of the experiment. They were housed individually in stainless steel cages and maintained at ~21°C on a 12:12-h light/dark cycle (lights off at 7:00 p.m.). Food was provided as a powder in glass jars held in the rats' cages by steel springs. Water and 0.3 M NaC1 were provided in glass bottles with stainless steel drinking spouts. The rats initially ate Purina Laboratory Chow (No. 5001) and drank tap water for 6 days so that they could adapt to laboratory conditions. They then received unlimited access to both deionized water and 0.3 M NaCI for another 6 days. After this baseline period, they continued to have access to deionized water and 0.3 M NaCI, but for 63 days, their chow was replaced with Ca2+-deficient (n=9), Na+-deficient (n=9) or AIN-76A control (n= 10) diet.
The deficient diets were modified versions of the AIN-76A formulation (1), prepared by Dyets Inc. (Bethlehem, PA) with mineral-free casein. AIN-76A diet contains per kilogram ~ 130 mmol Ca2+, 44 mmol Na +, and 92 mmol K +. The Na +-deficient diet was prepared by omission of NaC1 from the mineral mix, leaving <0.01 mmol/kg Na + . The Ca2+-deficient diet was made by substituting K2HPO,* for CaHPO4 (to maintain dietary P at ~129 mmol/kg) and, in order to reduce the resulting high K + content, substituting MgSO,, for K2SO,, and K-citrate. Magnesium concentrations were maintained constant by reducing MgO content (Table 1). This diet contained per kilogram, essentially 0 mmol Ca2+, 44 mmol Na +, and 92 mmol K +. Other minerals were supplied in the same concentrations as the AIN-76A (control) diet. Body weights and intakes of food (including spillage), water, and 0.3 M NaC1 were measured (-+ 1 g) daily. Differences between the three dietary groups were inferred from the results of mixed-design analyses of variance, with factors of Group and Days fed the diet. When the analyses produced significant interactions, differences between means on individual days were inferred from post hoc t-tests. All statistical tests were conducted using a probability cut-off of p<0.05. All values are given as means -+SEs. RESULTS Fischer-344 rats fed CaZ+-deficient diet gradually increased 0.3 M NaC1 intake over the 63-day test period (Fig. 1). Rats fed Ca2+-deficient diet drank significantly more NaCI than did rats fed control diet on every day after Day 11, and significantly more than did rats fed Na+-deficient diet on every day after Day 13 [Group × Day interaction, F(2,25)= 44.6, p<0.00001]. Rats fed control or Na +-deficient diet maintained relatively constant daily NaC1 intakes: Over the entire test period, those fed Na +-deficient diet drank slightly but consistently more 0.3 M NaCI than did those fed control diet (11.0_+0.3 ml vs. 8.0_+0.2 ml, p<0.01). Despite the large differences in 0.3 M NaCI intake, the diets had no effect on daily water intake [average for 63-day test: con-
113
114
I'()RDOFF
TABLE 1 MINERAL COMPOSITION OF AIN-76A CONTROL. Na + -DEFICIENT, AND Ca ~ * -DEFICIENT DIETS
Ingredient (g/kg Diet) Calcium phosphate, dibasic Potassium phosphate, monobasic Sodium chloride Potassium citrate, monohydrate Potassium sulfate Magnesium sulfate Magnesium oxide
AIN-76A Control
Na ~ Deficient
Ca-"* Deficient
17.50 0 2.59 7.70 1.82 0 0.84
17.50 0 0 7.70 1.82 0 0.84
0 17.50 2.59 0 0 1.267 0.416
The diets had in common (g/kg): casein (200), DL-methionine (3), cornstarch (150), sucrose (500), cellulose (50), corn oil (50), vitamin mix (10), choline bitartrate (2), manganous carbonate (0.1225), ferric citrate, USP (0.210), zinc carbonate (0.056), cupric carbonate (0.105), potassium iodate (0.00035), sodium selenite (0.00035), chromium potassium sulfate (0.01925). The remaining fraction of the mineral mix was provided by adding sucrose (10-15 g/kg diet).
75
50
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(3 Z
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25
0 30
20
"8 10
i
i
i
i
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i
i
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i
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I
20 v xzl 0 0 L
10 I
0
300
200 o~
>., z3 0
100
0
20 4O Days on Diet
60
FIG. 1. Intakes of 0.3 M NaC|, deionized water, and food, and body weight of Fischer-344 rats fed diets deficient in Ca2 ÷ or Na ÷ for 63 days. Prior to Day 0, all rats were fed chow.
trol d i e t = 15.3---0.2 ml, Na ~-deficient d i e t : i 7 . 0 : 0 . 2 ml, Ca 2 * -deficient diet = 15.8 ± 0.2 ml; F(2,25) = 1.21, NS]. All three groups decreased water intake significantly when they were transferred from Purina chow to semisynthetic diet (Day 0; Fig. l l, Food intake of the Ca 2 +-deprived rats was slightly but significantly less than that of the controls. Food intake of the group fed Na + -deficient diet was intermediate between, and not statistically different from, the other two groups [average for 63-day test: control d i e t = 1 3 . 6 _ 0 . 1 g, Na--deficient d i e t = 1 2 . 9 ± 0 , t g, Ca 2 * -deficient diet = 12.1 ± 0.1 g; F(2,25) = 3.78, p < 0 . 0 5 ] . Differences between food intakes of the three groups were not consistent over time [interaction of Groups x Days, F(124,1550)= 1.52, p < 0 . 0 5 ] , and probably reflected sporadic fluctuations in daily food intakes rather than a meaningful difference related to the treatments (Fig. 1). Rats fed Ca-" + -deficient diet weighed significantly less than those fed control or Na + -deficient diet after 40 days. The body weights of the control and Na ~ -deficient diet groups were almost identical. DISCUSSION
Fischer-344 rats deprived of dietary Ca 2 + ingested large volumes of 0.3 M NaC1. During the last few days of the study, they consumed 19.5 mmol/day NaC1, which was 6-7-fold more than rats fed control or Na+-deficient diet. Rowland and Fregly (8) showed that adrenalectomized Fischer-344 rats drink - 4 . 8 mmol/ day 0.3 M NaC1. Compared with this severe disruption of the ren i n - a n g i o t e n s i n - a l d o s t e r o n e system, it appears that Ca 2+ deprivation is a far more potent stimulus for inducing NaCI consumption. The results found here with Fischer-344 rats are similar to those found previously with Sprague Dawley rats (12). In both strains, 0.3 M NaCI intake begins to increase above that of controls after - 1 week of Ca 2 + deprivation. The rate of increase ( - 1 ml/day/day) was slightly lower in the Fischer-344 than Sprague Dawley strain, which is consistent with the inbred strain's slower growth (and thus lower demand for Ca 2 +). As is the case with Sprague Dawley rats (12), the high 0.3 M NaC1 intake of Ca 2 +-deprived Fiscber-344 rats was not due to nonspecific changes in food intake, water intake, or body weight: Both groups of mineral-deficient rats had normal water intakes and similar, small reductions in food intakes. Moreover, Ca 2 +-deprived rats did not differ reliably from controls in body weight until after 40 days on the diet but drank reliably more 0.3 M NaC1 after 11 days. There seems little reason to doubt that the mechanism controlling Ca 2 + -deprivation-induced NaCI intake in the Sprague Dawley strain is also present in the Fischer-344 strain. Compared with other studies of salt preference using Fischer344 rats (6-8), rats fed control diet in this study had higher daily intakes of 0.3 M NaCI. This may be because the Na + content of the AIN-76A control diet used here was less than that of most other maintenance diets [e.g., AIN-76A = 44 mmol/kg vs. Purina chow = - 6 7 mmol/kg (7)]. The high 0.3 M NaC1 intakes of rats fed the control diet may also explain why the effects of feeding Na+-deficient diet appeared relatively small. Nevertheless, the rats fed Na ÷-deficient diet drank more than sufficient additional 0.3 M NaC1 (0.90 mmol/day) to counteract the loss of Na ÷ from their diet (0.60 mmol/day). It is not known how Ca e ÷ deprivation affects NaC1 intake, or if Fischer-344 rats have an unusual Ca e+ metabolism. It is worthwhile noting, however, that the spontaneously hypertensive (SHR) strain, which has abnormally high NaC1 intake [e.g., (2,3)], has several deficiencies in Ca 2 ÷ metabolism, including low circulating Ca e ÷ concentrations, high concentrations of parathyroid hormone, hypercalciuria, and low bone Ca 2+ [e.g., (5, 11, 13); see (4) for a review]. It may be that the Fischer-344 rat spurns NaC1 because it has an inborn idiosyncrasy that refines
C A L C I U M D E P R I V A T I O N A N D NaC1 I N T A K E
115
some aspect o f Ca 2 ÷ metabolism. Indeed, differences in the regulation o f Ca 2 ÷ could potentially explain the differences in NaC1 intake among a variety o f species [see (10) for review]. Whatever
the explanation, the present results indicate that in the Fischer344 rat, the availability o f calcium is a far more pertinent stimulus for NaC1 intake than is the availability o f sodium.
ACKNOWLEDGEMENTS This work was supported by National Institutes of Health Grant DK40099. Expert technical assistance was provided by Patricia Ulrich, Fred Sandler, Michele Ewell and Rebecca Hughes. REFERENCES 1. Ad hoc Committee on Standards for Nutritional Studies. Second report of the ad hoc committee on standards for nutritional studies. J. Nutr. 110:1726; 1980. 2. Di Nicolantonio, R.; Mendelsohn, F. A. O.; Hutchinson, J. S. Sodium chloride preference of genetically hypertensive and normotensive rats. Am. J. Physiol. 245:R38-R44; 1983. 3. Henkin, R. I. Salt taste and salt preference in normal and hypertensive rats and humans. In: Kare, M. R.; Fregly, M. J.; Bernard, R. A., eds. Biological and behavioral aspects of salt intake. New York: Academic Press; 1980:367-396. 4. Lau, K.; Eby, B. The role of calcium in genetic hypertension. Hypertension 7:657-667; 1985. 5. McCarron, D. A.; Yung, N. N.; Ugoretz, B. A.; Krutzik, S. Disturbances of calcium metabolism in the spontaneously hypertensive rat. Hypertension 3:162-167; 1981. 6. Midkiff, E. E.; Fitts, D. A.; Simpson, J. B.; Bernstein, I. L. Absence of sodium chloride preference in Fischer-344 rats. Am. J. Physiol. 49:R438-R442; 1985. 7. Midkiff, E. E.; Fitts, D. A.; Simpson, J. B.; Bernstein, I. L. Atten-
8.
9.
10.
11.
12. 13.
uated sodium appetite in response to sodium deficiency in Fischer344 rats. Am. J. Physiol. 252:R562-R566; 1987. Rowland, N. E.; Fregly, M. J. Induction of an appetite for sodium in rats that show no spontaneous preference for sodium chloride solution-the Fischer 344 strain. Behav. Neurosci. 102:961-968; 1988. Rowland, N. E.; Fregly, M. J. Regulation of intakes of water and NaC1 solutions in Fischer 344 rats: Contrasts and comparisons between strains. Physiol. Behav. 44:461-467; 1988. Rowland, N. E.; Fregly, M. J. Sodium appetite: species and strain differences and role of renin-angiotensin-aldosterone system. Appetite 11:143-178; 1988. Schedl, H. P.; Wilson, H. D.; Horst, R. L. Calcium transport and vitamin D in three breeds of spontaneously hypertensive rats. Hypertension 12:310-316; 1988. Tordoff, M. G.; Ulrich, P. M.; Schulkin, J. Calcium deprivation increases salt intake. Am. J. Physiol. 259:R411-R419; 1990. Wright, G. L.; Rankin, G. O. Concentrations of ionic and total calcium in plasma of four models of hypertension. Am. J. Physiol. 243:H365-H370; 1982.
0031-9384/91 $3.00 + .00
Calcium Deprivation Increases NaC1 Intake of Fischer-344 Rats MICHAEL G. TORDOFF Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104-3308 Received 16 July 1990
TORDOFF, M. G. Calcium deprivation increases NaCl intake of Fischer-344 rats. PHYSIOL BEHAV 49(1) 113-115, 1991.Fischer-344 rats fed Ca2+-deficientdiet for 63 days increased intake of 0.3 M NaC1 solution from control levels of - 8 ml/day to >60 ml/day. During the same period, rats fed Na+-deficient diet drank ~11 ml/day. These results indicate that Fischer-344 rats, which generallyspurn NaCI, drink large amountsof it when Ca2+ deprived. Salt intake
Sodium
Strain differences
Calcium
FISCHER-344 rats differ from other strains used to study ingestive behavior in that they show little spontaneous intake of dilute NaC1 solution (6--8). Despite this, they respond to manipulations of the renin-angiotensin-aldosterone system such as adrenalectomy, dietary Na + restriction, or treatment with furosemide, deoxycorticosterone acetate, or angiotensin converting enzyme inhibitors [(7,8); reviews (9,10)]. Their response to these manipulations tends to be blunted relative to those of other strains, but it is still sufficient to satisfy Na + homeostasis. Recently, we found that a potent control of NaC1 intake is provided by some aspect of Ca2 + metabolism. Sprague DawIcy rats fed low-Ca2+ diets dramatically increase their voluntary NaC1 intake. These animals have normal plasma concentrations of Na +, aldosterone, and angiotensin I, and they retain Na + more efficiently than do controls (12). Given that neither the low NaC1 intake of Fischer-344 rats nor the high NaC1 intake of Ca2÷-deficient Sprague Dawley rats can easily be accounted for by dysfunctions of the renin-angiotensin-aldosteronesystem, it seemed worthwhile examining if Fischer-344 rats were sensitive to the effects of Ca2+ deprivation. METHOD The subjects were 28 male Fischer-344 rats, purchased from Charles River (Kingston, NY), weighing 67-88 g at the start of the experiment. They were housed individually in stainless steel cages and maintained at ~21°C on a 12:12-h light/dark cycle (lights off at 7:00 p.m.). Food was provided as a powder in glass jars held in the rats' cages by steel springs. Water and 0.3 M NaC1 were provided in glass bottles with stainless steel drinking spouts. The rats initially ate Purina Laboratory Chow (No. 5001) and drank tap water for 6 days so that they could adapt to laboratory conditions. They then received unlimited access to both deionized water and 0.3 M NaCI for another 6 days. After this baseline period, they continued to have access to deionized water and 0.3 M NaCI, but for 63 days, their chow was replaced with Ca2+-deficient (n=9), Na+-deficient (n=9) or AIN-76A control (n= 10) diet.
The deficient diets were modified versions of the AIN-76A formulation (1), prepared by Dyets Inc. (Bethlehem, PA) with mineral-free casein. AIN-76A diet contains per kilogram ~ 130 mmol Ca2+, 44 mmol Na +, and 92 mmol K +. The Na +-deficient diet was prepared by omission of NaC1 from the mineral mix, leaving <0.01 mmol/kg Na + . The Ca2+-deficient diet was made by substituting K2HPO,* for CaHPO4 (to maintain dietary P at ~129 mmol/kg) and, in order to reduce the resulting high K + content, substituting MgSO,, for K2SO,, and K-citrate. Magnesium concentrations were maintained constant by reducing MgO content (Table 1). This diet contained per kilogram, essentially 0 mmol Ca2+, 44 mmol Na +, and 92 mmol K +. Other minerals were supplied in the same concentrations as the AIN-76A (control) diet. Body weights and intakes of food (including spillage), water, and 0.3 M NaC1 were measured (-+ 1 g) daily. Differences between the three dietary groups were inferred from the results of mixed-design analyses of variance, with factors of Group and Days fed the diet. When the analyses produced significant interactions, differences between means on individual days were inferred from post hoc t-tests. All statistical tests were conducted using a probability cut-off of p<0.05. All values are given as means -+SEs. RESULTS Fischer-344 rats fed CaZ+-deficient diet gradually increased 0.3 M NaC1 intake over the 63-day test period (Fig. 1). Rats fed Ca2+-deficient diet drank significantly more NaCI than did rats fed control diet on every day after Day 11, and significantly more than did rats fed Na+-deficient diet on every day after Day 13 [Group × Day interaction, F(2,25)= 44.6, p<0.00001]. Rats fed control or Na +-deficient diet maintained relatively constant daily NaC1 intakes: Over the entire test period, those fed Na +-deficient diet drank slightly but consistently more 0.3 M NaCI than did those fed control diet (11.0_+0.3 ml vs. 8.0_+0.2 ml, p<0.01). Despite the large differences in 0.3 M NaCI intake, the diets had no effect on daily water intake [average for 63-day test: con-
113
114
I'()RDOFF
TABLE 1 MINERAL COMPOSITION OF AIN-76A CONTROL. Na + -DEFICIENT, AND Ca ~ * -DEFICIENT DIETS
Ingredient (g/kg Diet) Calcium phosphate, dibasic Potassium phosphate, monobasic Sodium chloride Potassium citrate, monohydrate Potassium sulfate Magnesium sulfate Magnesium oxide
AIN-76A Control
Na ~ Deficient
Ca-"* Deficient
17.50 0 2.59 7.70 1.82 0 0.84
17.50 0 0 7.70 1.82 0 0.84
0 17.50 2.59 0 0 1.267 0.416
The diets had in common (g/kg): casein (200), DL-methionine (3), cornstarch (150), sucrose (500), cellulose (50), corn oil (50), vitamin mix (10), choline bitartrate (2), manganous carbonate (0.1225), ferric citrate, USP (0.210), zinc carbonate (0.056), cupric carbonate (0.105), potassium iodate (0.00035), sodium selenite (0.00035), chromium potassium sulfate (0.01925). The remaining fraction of the mineral mix was provided by adding sucrose (10-15 g/kg diet).
75
50
I I ±,~"gl~mkV' ,~,'T ,,j'
(3 Z
t,o o
25
0 30
20
"8 10
i
i
i
i
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i
i
i
~
i
i
i
I
20 v xzl 0 0 L
10 I
0
300
200 o~
>., z3 0
100
0
20 4O Days on Diet
60
FIG. 1. Intakes of 0.3 M NaC|, deionized water, and food, and body weight of Fischer-344 rats fed diets deficient in Ca2 ÷ or Na ÷ for 63 days. Prior to Day 0, all rats were fed chow.
trol d i e t = 15.3---0.2 ml, Na ~-deficient d i e t : i 7 . 0 : 0 . 2 ml, Ca 2 * -deficient diet = 15.8 ± 0.2 ml; F(2,25) = 1.21, NS]. All three groups decreased water intake significantly when they were transferred from Purina chow to semisynthetic diet (Day 0; Fig. l l, Food intake of the Ca 2 +-deprived rats was slightly but significantly less than that of the controls. Food intake of the group fed Na + -deficient diet was intermediate between, and not statistically different from, the other two groups [average for 63-day test: control d i e t = 1 3 . 6 _ 0 . 1 g, Na--deficient d i e t = 1 2 . 9 ± 0 , t g, Ca 2 * -deficient diet = 12.1 ± 0.1 g; F(2,25) = 3.78, p < 0 . 0 5 ] . Differences between food intakes of the three groups were not consistent over time [interaction of Groups x Days, F(124,1550)= 1.52, p < 0 . 0 5 ] , and probably reflected sporadic fluctuations in daily food intakes rather than a meaningful difference related to the treatments (Fig. 1). Rats fed Ca-" + -deficient diet weighed significantly less than those fed control or Na + -deficient diet after 40 days. The body weights of the control and Na ~ -deficient diet groups were almost identical. DISCUSSION
Fischer-344 rats deprived of dietary Ca 2 + ingested large volumes of 0.3 M NaC1. During the last few days of the study, they consumed 19.5 mmol/day NaC1, which was 6-7-fold more than rats fed control or Na+-deficient diet. Rowland and Fregly (8) showed that adrenalectomized Fischer-344 rats drink - 4 . 8 mmol/ day 0.3 M NaC1. Compared with this severe disruption of the ren i n - a n g i o t e n s i n - a l d o s t e r o n e system, it appears that Ca 2+ deprivation is a far more potent stimulus for inducing NaCI consumption. The results found here with Fischer-344 rats are similar to those found previously with Sprague Dawley rats (12). In both strains, 0.3 M NaCI intake begins to increase above that of controls after - 1 week of Ca 2 + deprivation. The rate of increase ( - 1 ml/day/day) was slightly lower in the Fischer-344 than Sprague Dawley strain, which is consistent with the inbred strain's slower growth (and thus lower demand for Ca 2 +). As is the case with Sprague Dawley rats (12), the high 0.3 M NaC1 intake of Ca 2 +-deprived Fiscber-344 rats was not due to nonspecific changes in food intake, water intake, or body weight: Both groups of mineral-deficient rats had normal water intakes and similar, small reductions in food intakes. Moreover, Ca 2 +-deprived rats did not differ reliably from controls in body weight until after 40 days on the diet but drank reliably more 0.3 M NaC1 after 11 days. There seems little reason to doubt that the mechanism controlling Ca 2 + -deprivation-induced NaCI intake in the Sprague Dawley strain is also present in the Fischer-344 strain. Compared with other studies of salt preference using Fischer344 rats (6-8), rats fed control diet in this study had higher daily intakes of 0.3 M NaCI. This may be because the Na + content of the AIN-76A control diet used here was less than that of most other maintenance diets [e.g., AIN-76A = 44 mmol/kg vs. Purina chow = - 6 7 mmol/kg (7)]. The high 0.3 M NaC1 intakes of rats fed the control diet may also explain why the effects of feeding Na+-deficient diet appeared relatively small. Nevertheless, the rats fed Na ÷-deficient diet drank more than sufficient additional 0.3 M NaC1 (0.90 mmol/day) to counteract the loss of Na ÷ from their diet (0.60 mmol/day). It is not known how Ca e ÷ deprivation affects NaC1 intake, or if Fischer-344 rats have an unusual Ca e+ metabolism. It is worthwhile noting, however, that the spontaneously hypertensive (SHR) strain, which has abnormally high NaC1 intake [e.g., (2,3)], has several deficiencies in Ca 2 ÷ metabolism, including low circulating Ca e ÷ concentrations, high concentrations of parathyroid hormone, hypercalciuria, and low bone Ca 2+ [e.g., (5, 11, 13); see (4) for a review]. It may be that the Fischer-344 rat spurns NaC1 because it has an inborn idiosyncrasy that refines
C A L C I U M D E P R I V A T I O N A N D NaC1 I N T A K E
115
some aspect o f Ca 2 ÷ metabolism. Indeed, differences in the regulation o f Ca 2 ÷ could potentially explain the differences in NaC1 intake among a variety o f species [see (10) for review]. Whatever
the explanation, the present results indicate that in the Fischer344 rat, the availability o f calcium is a far more pertinent stimulus for NaC1 intake than is the availability o f sodium.
ACKNOWLEDGEMENTS This work was supported by National Institutes of Health Grant DK40099. Expert technical assistance was provided by Patricia Ulrich, Fred Sandler, Michele Ewell and Rebecca Hughes. REFERENCES 1. Ad hoc Committee on Standards for Nutritional Studies. Second report of the ad hoc committee on standards for nutritional studies. J. Nutr. 110:1726; 1980. 2. Di Nicolantonio, R.; Mendelsohn, F. A. O.; Hutchinson, J. S. Sodium chloride preference of genetically hypertensive and normotensive rats. Am. J. Physiol. 245:R38-R44; 1983. 3. Henkin, R. I. Salt taste and salt preference in normal and hypertensive rats and humans. In: Kare, M. R.; Fregly, M. J.; Bernard, R. A., eds. Biological and behavioral aspects of salt intake. New York: Academic Press; 1980:367-396. 4. Lau, K.; Eby, B. The role of calcium in genetic hypertension. Hypertension 7:657-667; 1985. 5. McCarron, D. A.; Yung, N. N.; Ugoretz, B. A.; Krutzik, S. Disturbances of calcium metabolism in the spontaneously hypertensive rat. Hypertension 3:162-167; 1981. 6. Midkiff, E. E.; Fitts, D. A.; Simpson, J. B.; Bernstein, I. L. Absence of sodium chloride preference in Fischer-344 rats. Am. J. Physiol. 49:R438-R442; 1985. 7. Midkiff, E. E.; Fitts, D. A.; Simpson, J. B.; Bernstein, I. L. Atten-
8.
9.
10.
11.
12. 13.
uated sodium appetite in response to sodium deficiency in Fischer344 rats. Am. J. Physiol. 252:R562-R566; 1987. Rowland, N. E.; Fregly, M. J. Induction of an appetite for sodium in rats that show no spontaneous preference for sodium chloride solution-the Fischer 344 strain. Behav. Neurosci. 102:961-968; 1988. Rowland, N. E.; Fregly, M. J. Regulation of intakes of water and NaC1 solutions in Fischer 344 rats: Contrasts and comparisons between strains. Physiol. Behav. 44:461-467; 1988. Rowland, N. E.; Fregly, M. J. Sodium appetite: species and strain differences and role of renin-angiotensin-aldosterone system. Appetite 11:143-178; 1988. Schedl, H. P.; Wilson, H. D.; Horst, R. L. Calcium transport and vitamin D in three breeds of spontaneously hypertensive rats. Hypertension 12:310-316; 1988. Tordoff, M. G.; Ulrich, P. M.; Schulkin, J. Calcium deprivation increases salt intake. Am. J. Physiol. 259:R411-R419; 1990. Wright, G. L.; Rankin, G. O. Concentrations of ionic and total calcium in plasma of four models of hypertension. Am. J. Physiol. 243:H365-H370; 1982.