Kidney International, Vol. 20 (1980), pp.

92—96

Acute hypercalcemic hypertension in man: Role of

hemodynamics, catecholamines, and renin
CLAUDIO MARONE, CARLO BERETTA-PICCOLI, and PETER WEIDMANN

Medizinische Poliklinik, University of Berne, Switzerland

Acute hypercalcemic hypertension in man: Role of hemodynamics, Calcium is an important factor in the regulation of blood
catecholamines, and renin. The effect of acute hypercalcemia on blood pressure. It plays a central role in the coupling between
pressure, blood volume, hemodynamic parameters, plasma norepineph- excitation and contraction of striated and vascular smooth
rifle, epinephrine, dopamine, renin, and aldosterone concentrations was
investigated. After 1 hour of equilibration, 10 patients received an muscle cells [1]. Moreover, variations in the concentration of
infusion of calcium gluconate in 5% dextrose (calcium 15 mg/kg of body calcium in the blood may be accompanied by parallel changes in
wt in 3 hours). The calcium infusion increased the mean serum calcium blood pressure. A rapid reduction of serum calcium concentra-
from 8.7 to 13.0 mg/dl, the systolic blood pressure from 144 10 to 184 tion induces hypotension in man [2, 31 and in the experimental
(5EM) 12 mm Hg (P < 0.001), the diastolic pressure from 78 4 to 93
5 mm Hg (P < 0.01). The plasma volume was decreased by 9% (P < animal [4]. Conversely, both acute [5, 6] or chronic forms of
0.001), whereas the hematocrit was increased (P < 0.05). Heart rate and hypercalcemia [7—12] may be associated with hypertension. The
cardiac output remained unchanged. Total peripheral resistance was mechanism by which excess calcium induces hypertension is
increased from 1643 223 to 2256 387 dynesec/cm5 (P < 0.05). The still unclear. Theoretically, hypercalcemia could influence
plasma epinephrine concentration rose from 4.5 0.7 to 6.9 1.2 ng/dl blood pressure by a direct action on the vascular muscle cells;
(P < 0.01). The plasma norepinephrine concentration was unchanged
after 2 hours and increased only slightly after 3 hours of calcium or its cardiovascular effect could be mediated by other blood-
infusion. Plasma renin, aldosterone, and dopamine concentrations were pressure-regulating factors such as the renin-angiotensin-aldos-
not significantly changed. These findings demonstrate that acute hyper- terone axis, the sympathetic nervous system, and circulatory
calcemic hypertension is mediated by an increase in peripheral vascular volume.
resistance. Hypercalcemic hypertension may be induced by a direct
effect of calcium on blood vessels; calcium-mediated increase in adrenal Plasma renin levels during acute hypercalcemia in man are
epinephrine release may play a mild contributory role, and plasma unchanged or slightly decreased [6, 11, 12]. Only few data are
volume contraction, an inhibitory role. available on the hemodynamic characteristics of hypercalcemic
hypertension [13, 141. Moreover, plasma and urinary catechol-
Hypertension hypercalcemique aiguë chez I'homme: Role des facteurs
hemodynamiques, des catécholamines, et de Ia refine plasmatiques.
amines and blood volume have not been evaluated in this
L'effet de l'hypercalcémie aigue sur Ia pression artérielle, le volume condition. Therefore, the present study was undertaken to
sanguin, les paramètres hCmodynamiques, Ia norepinéphrine, l'épi- investigate the role of plasma renin, aldosterone, and catechol-
nephrine, Ia dopamine, Ia rénine, et l'aldostérone plasmatiques a été amines levels, plasma and blood volume, and important hemo-
étudié. Après une heure d'équilibration, 10 sujets ont recu une perfu- dynamic parameters in the genesis of acute hypercalcemic
sion de gluconate de calcium dans du dextrose 5% (calcium, 15 mg/kg
de poids en 3 heures). La perfusion de calcium a augmentC Ia concentra- hypertension in man.
tion sérique moyenne de calcium de 8,7 a 13,0 mg/dl, Ia pression
artCrielle systolique de 144 10 a 184 (sEM) 12mm Hg (P < 0,001), Methods
Ia pression diastolique de 78 4 a 93 5 mm Hg (P < 0,01). Le volume
plasmatique a diminué de 9% (P < 0,001) alors que l'hématocrite a Studies with calcium infusion. Because of our previous
augmenté (P < 0,05). La fréquence cardiaque et Ic debit cardiaque sont demonstration of pressor responses to acute hypercalcemia in
restCs inchangCs. Les resistances totales pCripheriques ont augmente de subjects with or without various degrees of renal failure [6], we
1643 223 a 2256 387 dynesec/cm5 (P < 0,05). La concentration
plasmatique de norepinephrine n'était pas modifiée aprés 2 heures et again asked subjects with normal or mildly impaired kidney
n'a que peu augmentC après trois heures de perfusion de calcium. Les function to participate in a study. During 1.5 years of recruit-
concentrations plasmatiques de rénine, d'aldostérone et de dopamine ment in the outpatient and inpatient departments of our hospi-
n'ont pas ete significativement modifiées. Ces constatations montrent tal, ten subjects, aged 19 to 71 years, volunteered and gave
que l'hypertension aiguC hypercalcémique a pour mCdiateur une aug- informed consent to undergo the investigations described be-
mentation des resistances vasculaires périphériques. L' hypertension
hypercalcémique peut étre déterminée par un effet direct de calcium sur low. They were six patients with normal kidney function (serum
les vaisseaux; l'augmentation de Ia liberation d'epinephrine par les creatinine, < 1.3 mg/dl; 51Cr-EDTA constant infusion clearance
surrénales, qui a le calcium pour médiateur, peutjouer un role adjuvant [15], > 95 mlIminl.73 m2) and four with slightly impaired
faible et Ia contraction du volume plasmatique un rOle inhibiteur. kidney function (serum creatinine, 2.2 to 2.8 mg/dl; 5tCr-EDTA
constant infusion clearance, 24 to 36 ml/min1.73 m2). Diag-
Received for publication May 6, 1980 noses were chronic glomerulonephritis in four patients (biopsy-
and in revised form October 1, 1980 proven in three patients), and chronic interstitial nephritis (N =
0085-2538/81/0020-0092 $01.00 1), pyelonephritis (N = 1), polycystic kidney disease (N = 1),
© 1981 by the International Society of Nephrology unilateral renal cysts (N = 1) and unilateral renal hypoplasia (N

92
 Hypercalcemic hypertension 93
14
pressure were monitored every 10 to 15 mm throughout the
E
entire procedure. Blood samples for determination of plasma
12
calcium (by autoanalyzer), sodium, potassium (by flame pho-
tometer), phosphate (by colorimeter), protein (by the Biuret
10
method), renin activity, aldosterone, norepinephrine, epineph-
rifle, and dopamine levels were collected, and cardiac output
8 (six patients) was measured immediately before and 2 and 3
210 - hours after starting the calcium infusion. Blood and plasma
volumes were determined by a radioisotope dilution technique
190 using '311-albumin [16] before and at the end (3 hours) of the
** calcium infusion.
170
Studies with dextrose infusion. To evaluate possible calcium-
0) * Systolic independent influences of the infusion procedure on blood
o 150- pressure, pulse rate, plasma volume, and endocrine parame-
• Diastolic ters, three additional patients were studied. Their ages ranged
V between 58 and 73 years, and their serum creatinine concentra-
130
m tions, between 1.1 and 2.3 mgldl (mean 1.7 0.3 mg/dl).
110
Following the 1-hour equilibration period (as above), these
patients received an i.v. infusion of 500 ml of 5% dextrose
without calcium; all measurements specified above were ob-
90-
tained except for cardiac output. Informed consent was ob-
tained. as in the former group of patients.
70
Special analytical procedures. Plasma renin activity and
0 1 2 3 aldosterone were determined by radioimmunoassay [17, 18],
Duration of calcium infusion, hr and plasma norepinephrine, epinephrine and dopamine were
Fig. I. Serum calcium and blood pressure before and during i.v. determined by radioenzymatic assay [19], as reported previous-
calcium infusion. Asterisks denote a significant difference from control ly from our laboratory [16, 20]. Intraarterial pressure was
conditions: < 0.05; ** < 0.01; *** < 0.001. determined with a Statham P23 Db strain gauge transducer and
registered on a Hellige three-channel ink recorder.
Cardiac output was determined by the Fick principle using
= 1). An additional patient was evaluated following an episode oxygen saturation. Oxygen consumption was estimated with
of hematuria but symptoms had already disappeared and no the tables of Fleisch [21]. Total peripheral resistance was
cause was found. Blood pressure was normal ( 140/90 mm Hg) calculated from cardiac output and intraarterial pressure.
in eight patients and mildly elevated in two (diastolic 94 and 95 Analysis of variance and (if a statistical significance was
mm Hg, respectively). There was no history or evidence of present) two-tailed Student's t test for paired data were used for
stroke, heart failure, heart block, major arrhythmias, other the statistical comparison of values before and during the
cardiovascular complications, or extrarenal organ disease. Nei- experimental procedure.
ther of the two female patients was on oral contraceptive drugs.
Six patients agreed to participate in the entire procedure; the Results
remaining four gave the consent for most of the procedure, Studies with calcium infusion. Calcium infusion increased
except for the pulmonary artery catheterization and the mea- serum calcium from 8.7 (sEM) 0.2 to 13.0 0.5 mg/dl (P <
surement of cardiac output. 0.001); systolic blood pressure, from 144 10 to 184 12 mm
The study started at 8 A.M. The patients rested in the supine Hg (P <0.001); and diastolic blood pressure, from 78 4 to 93
position. A microcatheter (Pulmocath) was inserted percutane- 5 mm Hg (P < 0.01) (Fig. 1). The hypertensive response was
ously, under local anesthesia, into an antecubital vein and especially marked for systolic blood pressure, which was
floated under pressure monitoring to the pulmonary artery. A increased by more than 20 mm Hg in each patient. Diastolic and
second catheter was introduced percutaneously into a brachial mean blood pressures were also consistently increased during
artery, for direct monitoring of arterial pressure. Both catheters calcium infusion. Pressor responses were comparable between
served to collect blood samples for the assessment of cardiac subjects with normal or mildly impaired renal function ( mean
output. In addition, an i.v. cannula was inserted in each arm; blood pressure, +27 (sEM) 8 vs. +21 4%), and no
one was used to collect blood samples for various determina- consistent difference was noted between subjects whose basal
tions, and the cannula on the contralateral arm was used for preinfusion blood pressure was normal ( diastolic blood pres-
infusions. Following these preparatory steps, an i.v. infusion of sure, + 15 4 mm Hg) or slightly increased (z diastolic blood
5% dextrose in water was started and maintained at a minimal pressure + 5 and + 20 mm Hg, respectively). Figure 2 illustrates
rate (50 ml/hr) for 1 hour of equilibration. At the end of this the mean changes in blood pressure as related to the alterations
equilibration period, basal measurements were obtained, and in serum calcium. The increase in blood pressure became
the dextrose infusion was replaced by an infusion of calcium significant when serum calcium was increased by 1 to 2 mg/dl (P
gluconate in 5% dextrose solution. A total of 15 mg of calcium <0.05).
per kilogram of body weight, dissolved in 500 ml of dextrose Serum phosphorus was also increased during calcium infu-
solution, was infused for 3 hours. Heart rate and intraarterial sion (from 2.6 0.3 to 4.2 0.3 mg!dl, P < 0.001). Plasma
94 Marone et a!

A Systolic
• Mean
.
.2Cri
0—i
>
90
• Diastolic
2
Th
m
5
80
:: 60
--i
'a0'
E'
30-
.E
a.
50

E
L5 80
a,
70
i.8 60
0
I
20-
cH 6

10
'
5

2800 -

*
0 2400

OOtol lto2 2to3 3to4 4to5

.
>5
.9-'a 2000-
Serum calcium, mg/dI
Fig. 2. Relationship between changes in blood pressure and increments
a.
in serum calcium during iv. calcium infusion. 1600-

0 1 2 3
sodium (138 1 vs. 136 2 mEq/liter) and potassium (3.8
Duration of calcium infusion, hr
0.2 vs. 3.9 0.1 mEq/liter) remained unchanged during calcium
infusion. Fig. 3. Plasma and blood volume and hemodynamic indices before and
during calcium infusion. Asterisks denote significant difference from
During calcium infusion, blood volume decreased from 86.6 control conditions: * < 0.05; *** < 0.001.
1.8 to 81.5 2.5 mllkg of lean body mass (LBM) (P < 0.05)
and plasma volume from 54.4 2.5 to 49.5 2.8 mi/kg of LBM
(P <0.001) (Fig. 3). Mean hematocrit was increased from 37.2 Studies with dextrose infusion. In three subjects who re-
2.4 to 39.4 2.8% (P < 0.05), and total serum protein rose ceived an i.v. infusion of dextrose only, blood pressure was
from 6.3 0.2 to 6.7 0.3 g/dl (not significant). Heart rate (69 149/88 12/5 mm Hg before the infusion and remained
3 vs. 65 3 beats/mm) and cardiac output (5.0 0.5 vs. 4.8 unchanged at 2 (143/88 12/7 mm Hg) and 3 hours (143/88
0.5 liter/mm) were not significantly changed, whereas total 12/7mm Hg) of infusion. Plasma epinephrine (4.4 1.2 vs. 2.7
peripheral resistance was increased from 1643 223 to 2256 1.1 vs. 4.2 2.3 ngldl), norepinephrine (31.8 12.7 vs. 30.2
387 dynesec-cm5 (P < 0.05). 15.5 vs. 34.8 23.7 ng/dl), dopamine, renin activity,
Plasma epinephrine concentration increased progressively aldosterone, calcium, phosphorus, sodium, potassium, and
during calcium infusion; changes were significant both at 2 and protein levels, hematocrit, plasma and blood volume, as well as
3 hours of infusion (P < 0.05 and P < 0.01, respectively) (Table pulse rate, remained also unchanged during dextrose infusion.
1). Plasma norepinephrine levels were unchanged after 2 hours
of infusion, but a minimal although significant increase (P < Discussion
0.05) was noted after 3 hours. Plasma dopamine, renin, and In this study the hemodynamic profile during acute elevation
aldosterone were not significantly altered. Calcium infusion of serum calcium concentration (+ 4.3 mgldl) was characterized
was not associated with adverse symptoms; only one patient by increases in blood pressure (P < 0.001) and total peripheral
complained about fatigue 2 to 3 hours after the infusion. vascular resistance (P < 0.05), whereas cardiac output and

Table 1. Effect of acute hypercalcemia on plasma catecholamine, renin, and aldosterone levels"
Plasma Plasma Plasma Plasma
. epinephrine norepinephrine dopamine PRA aldosterone
Duration of calcium
infusion, hr ng/dl ng/dl ngldl ng/ml/hr ng/dl
0 (control) 4.5 0.7 19.8 4.3 11.6 1.2 2.6 0.8 6.1 1.0
2 59 19.2 3.9 12.4 1.5 2.1 0.7 6.9 1.7
3 6.9 1.2" 23.0 4.6" 12.3 1.3 1.9 0.6 7.1 1.9
a Values are the means SEM.
b p < 0.05, compared with values before calcium infusion.
P < 0.01, compared with values before calcium infusion.
 Hypercalcemic hypertension 95

heart rate were unaltered. A similar observation was made in those of others [12]. An increase in circulating aldosterone
anesthetized dogs [22], and also described as a preliminary following calcium infusion was described in patients with
observation in one case [13]. It is known that calcium may terminal renal failure [35], but in vitro studies revealed only an
increase the contractility of both the heart [14, 231 and the indirect relationship between calcium and aldosterone secretion
peripheral blood vessels [24, 25]. In previous studies in man, [36].
acute hypocalcemia was associated with a decreased cardiac The observed decrease in plasma volume (P < 0.001) and
output [26]; whereas calcium infusion was reported to cause an increase in hematocrit (P < 0.05) during acute hypercalcemia in
increased cardiac output [14] and a slowing of heart rate [231. our patients are consistent with a mild fluid loss from the
The latter studies differ from the present protocol in that the vascular compartment, which cannot be explained by blood
duration of calcium infusion was very short (5 to 6 mm) and the sampling. Volume contraction following calcium infusion could
degree of hypercalcemia milder, and no increase of blood result from an extravascular shift secondary to a high blood
pressure occurred in one of them [23]. Nevertheless, it appears pressure-induced increase in capillary filtration pressure, or
possible that acute hypercalcemic hypertension is initiated by a from an augmented renal sodium diuresis [37]. Whatever the
very short phase with increased cardiac output [14] and rapidly exact underlying mechanisms, it is possible that intravascular
progresses to a hemodynamic pattern with elevated peripheral volume contraction may partly counteract the pressor mecha-
vascular resistance. Moreover, because an increase in blood nism of acute hypercalcemia in man.
pressure induced by peripheral vasoconstriction should normal- Taken together, these findings suggest that acute hypercalce-
ly be associated with a compensatory decrease in cardiac mic hypertension is mediated by an increase in peripheral vas-
output, the lack of the latter adaptive reaction in our patients cular resistance. This hypertension may be induced by a di-
may in fact indicate an inappropriately high cardiac output rect effect of calcium on the cardiovascular system. A calcium-
during acute hypercalcemia. mediated increase in adrenal epinephrine release may play a
Calcium is essential for the contraction of striated and contributory role; and a reduced plasma volume, an inhibitory
vascular smooth muscle cells. It is possible, therefore, that the role.
cardiovascular changes that occur during hypercalcemia are at
least partly owing to a direct effect of the cation of the vascular Acknowledgments
muscle cells [27]. It is equally possible that hypercalcemia
increases the sensitivity of the cardiovascular system to the This work was supported by the Swiss National Science Foundation.
action of vasoconstrictor substances; but laboratory data do not Miss L. Bollinger, Mrs. G. Haueter, Miss U. Litschi, Miss R. Mosi-
mann, and Miss D. Riediker provided technical assistance.
support such a concept [25, 281.
The release of catecholamines is calcium dependent [291, and Reprint requests to Dr. P. Weidmann, Medizinische Universitäts-
experimental data have suggested that increased calcium ion Poliklinik, Freiburgstrasse 3, 3010 Bern, Switzerland.
activity may augment the release of epinephrine from the
adrenal medulla [30, 31] and of norepinephrine from the sympa- References
thetic nerve endings [32, 33]. Therefore, it appears possible that
1. BOHR DF: Vascular smooth muscle updated. Circ Res 32:665—672.
the increased plasma epinephrine concentrations during hyper- 1973
calcemia in our patients were due to a direct stimulatory effect 2. SHACKNEY S, HASSON J: Precipitous fall in serum calcium, hypoten-
of calcium on adrenal medullary discharge. Plasma norepineph- sin, and acute renal failure after intravenous phosphate therapy for
rime concentrations, which may be an approximate index of hypercalcemia. Ann Intern Med 66:906—916, 1967
sympathetic nervous activity, remained unchanged after 2 3. LLACH F, WEIDMANN P, REINHART R, MAXWELL MH, COBURN
hours of calcium infusion in these patients, but a minor increase JW, MASSRY SG: Effect of acute and long.standing hypocalcemia
on blood pressure and plasma renin activity in man. J Clin
was noted at 3 hours. The latter variation could be spontaneous Endocrinol Metab 38:841—847, 1974
or calcium dependent [32, 33]. It appears probable that the 4. MAXWELL GM, ELLIOT RB, ROBERTSON E: The effect of Na2-
sympathetic system does not play a prime pathogenic role in EDTA-induced hypocalcemia upon the general and coronary hemo-
dynamics of the intact animal. Am Heart J 66:82—87, 1963
acute hypercalcemic hypertension. Increases in plasma epi- 5. MOORE WT, SMITH LH JR: Experience with a calcium infusion test
nephrine during calcium infusion did not exceed the upper limit in parathyroid disease. Metabolism 12:447—451, 1963
of the normal range [34]; and due to its high affinity to beta 6. WEIDMANN P, MASSRY SG, COBURN JW, MAXWELL MH, ATLE-
adrenergic receptors, an augmented release of this catechol- SON J, KLEEMAN CR: Blood pressure effect of acute hypercalce-
amine would be expected to stimulate heart rate and cardiac mia. Ann Intern Med 76:741—745, 1972
7. HELLSTR0EM J, BIRKE G, EDVALL CA: Hypertension in hyperpara.
output. The absence of "hyperkinetic circulatory pattern" thyroidism. BrJ Urol 30:13—24, 1958
following 2 to 3 hours of calcium infusion in our patients does 8. EARLL JM, KURTZMAN NA, MOSER RH: Hypercalcemia and hyper-
not exclude a mild cardiac stimulatory effect of epinephrine, but tension. Ann Intern Med 64:378—381, 1966
its part in the mechanism of acute hypercalcemic hypertension 9. ROSENTHAL FD, ROY S: Hypertension and hyperparathyroidism.
may be contributory rather than dominant. Br Med J 4:396—397, 1972
10. BRINTON OS, JUBIZ W, LAGERQUIST LD: Hypertension in primary
Because plasma renin levels were not significantly altered hyperparathyroidism: The role of the renin-angiotensin system. J
during calcium infusion, this factor could not account for acute Clin Endocrinol Metab 41:1025—1029, 1975
hypercalcemic hypertension in our patients. Previous studies in 11. EPSTEIN S, SAGEL J, BRODOVCKY H, TUFF S, EALES L: Absence of
man revealed unchanged [6, 11] or slightly decreased [12] levels an acute effect of calcium or parathyroid hormone administration
on plasma renin activity in man. Gun Sci Mo! Med 50:79—8 1, 1976
of circulating renin following calcium infusion, as well as 12. KIscH ES, DLUHY RG, WILLIAMS GH: Regulation of renin release
unaltered plasma renin activity during acute hypocalcemia [31. by calcium and ammonium ions in normal man. J Clin Endocrinol
Plasma aldosterone levels were also stable in our patients and in Metab 43:1343—1350, 1976
96 Marone et a!

13. LIFSCHITZ MD, PAK Cyc, HENNEMAN D, JOWSEY J, PILCH Y, 25. FROHLICH ED, SCOTT JB, HAnDY FJ: Effect of cations on resistance
BARTTER FC: Treatment of osteoporosis with calcium infusions. and responsiveness of renal and forelimb vascular beds. Am J
Trans Assoc Am Phys 83:254—266, 1970 Physiol 203:582—587, 1962
14. M0RI K: The effects of infusion of calcium and magnesium ions on 26. BUNKER JP, BENDIXEN HH, MURPHY AJ: Hemodynamic effects of
the cardiovascular system in man. Jpn Heart J 19:226—235, 1978 intravenously administered sodium citrate. N Engi J Med 266:372—
15. VORBURGER C, RIEDWYL H, REUBI FC: Vergleichende Studien 377, 1962
zwischen den renalen Clearances von 51Cr-EDTA, Inulin und 27. FABIATO A, FABIATO F: Calcium and cardiac excitation-contraction
Natriumthiosulfat beim Menschen. K/in Wochenschr 47:415—420, coupling, Ann Rev Physiol 41:473-484, 1979
1969 28. FARMER JB, CAMPBELL 1K: Calcium and magnesium ions: influence
16. WEIDMANN P, DE CHATEL R, SCHIFFMANN A, BACHMANN E, on the response of an isolated artery to sympathetic nerve stimula-
BERETTA-PICCOLI C, Rui FC, ZIEGLER WH, VETTER W: Interre- tion, noradrenaline and tyramine. BrJ Pharmacol 29:319—328, 1967
lations between age and plasma renin, aldosterone and cortisol, 29. RUBIN RP: The role of calcium in the release of neurotransmitter
urinary catecholamines, and the body sodium/volume state in substances and hormones. Pharmacol Rev 22:389—428, 1970
normal man. K/in Wochenschr 55:725—733, 1977 30. DOUGLAS WW, RUBIN RP: The role of calcium in the secretory
17. SEALEY JE, AERTEN-BANES J, LARAGH JH: The renin system: response of the adrenal medulla to acetylcholine. J Physiol (Lon-
variations in man measured by radioimmunoassay and bioassay. don) 159:40—57, 1961
Kidney mt 1:240—253, 1972 31. GREENBERG R, KOLEN CA: Effects of acetylcholine and calcium
18. VETTER W, VETrER H, SIEGENTHALER W: Radioimunoassay for ions on the spontaneous release of epinephrine from catecholamine
aldosterone without chromatography: II. Determination of plasma granules. Proc Soc Exp Biol Med 121:1179—1184, 1966
aldosterone.
Acta Endocrinol (Copenh) 74:558—567, 1973 32. KIRKEPAR SM, MISU Y: Release of noradrenaline by splenic nerve
19. DA PRADA M, ZUERCHER G: Simultaneous radioenzymatic determi- stimulation and its dependence on calcium. J Physiol (London)
nation of plasma and tissue adrenaline, noradrenaline and dopa- 188:219—234, 1967
mine within the femtomole range. Life Sci 19:1161—1174, 1976 33. BOULLIN DJ: The action of extracellular cations on the release of
20. WEIDMANN P, BERETTA-PICCOLI C, ZIEGLER H, KEUSCH 0, the sympathetic transmitter from peripheral nerves. J Physio!
GLUECK Z, REUBI FC: Age versus urinary sodium for judging (London) 189:85—99, 1967
renin, aldosterone. and catecholamine levels: Studies in normal 34. WEIDMANN P, BERETTA-PICCOLI C, KEUSCH G, GLUECK Z,
subjects and patients with essential hypertension. Kidney mt MUJAGIC M, GRIMM M, MEIER A, ZIEGLER W: Sodium-volume
14:619—628, 1978 factor, cardiovascular reactivity and hypotensive mechanism of
21. FLEISCH A: Le métabolisme basal standard et sa determination au diuretic therapy in mild hypertension associated with diabetes
moyen du "Metabocalculator". He/v Med Acta 18:23—44, 1951 mellitus. Am J Med 67:779—784, 1979
22. SIALER 5, MCKENNA DH, CoRLiss RJ, ROWE OR: Systemic and 35. OLGAARD K, MADSEN 5, HAMMER M, LADEFOGED J: Calcium
coronary hemodynamic effects of intravenous administration of dependent aldosterone secretion in anephric and nonnephrecto-
calcium chloride. Arch mt Pharmacodyn Ther 169:177—184, 1967 mized patients on regular hemodialysis. J Clin Endocrinol 46:740—
23. SHINER PT, HARRIS WS, WEISSLER AM: Effect of acute changes in 746, 1978
serum calcium levels in the systolic time intervals in man. Am J 36. KOTCHEN TA, GALLA JH, LUKE RG: Effects of calcium on renin
Cardiol 24:42—48, 1969 and aldosterone in the rat. Am J Physio/ 232:E388—E393, 1977
24. HADDY FJ, SCOTT JB, FL0RI0 MA, DAUGHERTY RM, HUIZENGA 37. SUKI WN, EKNOYAN G, RECTOR FC JR, SELDIN DW: The renal
JN: Local vascular effects of hypokalemia, alkalosis, hypercalce- diluting and concentrating mechanism in hypercalcemia. Nephron
mia, and hypomagnesemia. Am J Physiol 204:202—212, 1963 6:50—61, 1969