ENDOCRINE RESFARCH COMMUNICATIONS, 3 ( 5 ) , 257-272 (1976)
CIRCADIAN VARIATIONS OF THE URINARY EXCRETION OF CATECHOLAMINES A N D ELECTROLYTES?
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6. Faucheux*, 0. Kuchel, J.L. Cuche**, F.H. Messerli***, N.T. B U U , A. Barbeau and J . Genest. Clinical Research I n s t i t u t e of Montreal, Laboratory o f the Sympathetic Nervous System, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7. *Present address: 6. Faucheux,Ph.D., I.N.S.E.R.M. -U-118, 29 rue Wilhem, Paris 75016, FRANCE. **Present address: J.L. Cuche,M.D., I.N.S.E.R.M. -U-27, Centre Medico-Chirurgical Foch, Suresnes 92150, FRANCE. ***Present address: F.H. Messerli,M.D., Medical P o l i c l i n i c , University Medical School, Bern, SWITZERLAND. ABSTRACT
Concomitant measurements of c i r c a d i a n v a r i a t i o n s i n t h e urinary excretion of dopamine ( D A ) , homovanillic acid ( H V A ) , norepinephrine ( N E ) , epinephrine ( E ) as well as of c r e a t i n i n e , sodium and potassium under controlled d i e t a r y conditions d u r i n g r e l a t i v e physical and emotional r e s t i n 13 volunteers have shown t h a t maximum excretion of a l l these substances occurred in t h e afternoon period between 14:30h and 18:00h, and minimum excretion in t h e morning between 4:OOh and 5:OOh. The changes were i n some cases progressive from one c o l l e c t i o n period t o t h e o t h e r , and synchronized f o r N E and E . DA and HVA excretions f l u c t u a t e d from s u b j e c t t o s u b j e c t . Excretory rhythms of sodium and potassium were found t o be s i m i l a r t o those of t h e catecholamines. This can be explained by diurnal changes in renal blood flow and d i f f e r e n t renal excretory mechanisms of catecholamines. None of t h e catecholamines correl a t e d with t h e urinary volume b u t urinary NE and E p o s i t i v e l y corr e l a t e d with urinary c r e a t i n i n e , urinary NE and E w i t h urinary DA and urinary sodium w i t h urinary E . There a r e some common p a t t e r n s in t h e diurnal rhythms o f catecholamines and e l e c t r o l y t e s b u t t h e i r i n t e r r e l a t i o n s h i p i s d i f f e rent f o r individual catecholamines.
t Reprints requests:
Otto Kuchel, M.D., Montreal , Quebec, Canada H2W 1R7.
110 Pine Avenue West,
257 Copyright 0 1976 by Marcel Dekker, Inc. All Rights Reserved Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher.
FAUCHEUX ET AL.
258
Circadian variations have been reported f or the catecholamines dopamine (DA) (1-4) (and i t s main metabolite homovanillic acid (HVA) (4-6) ) , norepinephrine (NE)
, and epinephrine
( E ) (4,7-12)
,
nonetanephrine and vanillylmandelic acid (VMA) (13) as well as for urinary electrolytes (14).
Different results have been obtained in
these studies , however, probably because of differ ent protocols and
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experimental methods, such as dif fer ent durations of urine collections and changes in body position.
Among the many variables, the
relationship between e le c t rol yte and catecholamine excretion i s of special i n t e r e s t since a relationship between the urinary excretion of NE and particularly OA and sodium has
been demonstrated during
upright posture (15) and sodium-load-induced volume expansion ( 1 6 ) . I t i s therefore important t o study concomitantly in the same subj e c t the excretion of catecholamines and electrolytes during bed r e s t , eliminating a l l the e ffe c ts of upright posture and of str essful stimuli and under controlled dietary conditions.
The main ob-
j e ct i ve of t h i s study was t o determine the excretion patterns of three catecholamines (DA, NE, E ) , one of t h e i r metabolites ( H V A ) , and urinary electrolytes (sodium and potassium) and t h e i r interrelationships.
Collection periods were relatively shorter than in
most previous studies. MATERIALS AND METHODS
Thirteen healthy volunteers ( 2 females and 11 males) between the age of 19 and 53 years (26 tory were chosen f o r the study.
*
2 years) with a normal medical his-
Complete physical examination re-
259
DIURNAL RHYTHM OF CATECHOLAMINES
vealed no a b n o r m a l i t i e s , t h e b l o o d pressure was always under 135/90 mmHg and t h e usual l a b o r a t o r y b l o o d and u r i n e t e s t s were w i t h i n n o r mal l i m i t s .
Women were i n v e s t i g a t e d i n t h e f i r s t h a l f o f t h e i r
menstrual c y c l e s and none o f them r e c e i v e d o r a l c o n t r a c e p t i v e s f o r a t l e a s t 3 months p r i o r t o t h e study. The s u b j e c t s were a d m i t t e d t h e evening p r i o r t o t h e day of t h e study i n t o a q u i e t a i r c o n d i t i o n e d p h y s i o l o g y room w i t h a s t a b l e Endocr Res Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
a i r temperature (22OC), and were asked t o a v o i d any undue s t r e s s e s . They were asked t o s t a y i n bed d u r i n g t h e whole 24h i n v e s t i g a t i o n t o a v o i d any posture-induced v a r i a t i o n s .
They s l e p t between 23:OOh
and 8:OOh and were awake d u r i n g t h e day-time,
spending t h e i r t i m e
r e a d i n g and watching t e l e v i s i o n . The s u b j e c t s i n g e s t e d a d a i l y d i e t c o n t a i n i n g 135 mEq o f sodium and 90 mEq o f potassium, which had been s t a r t e d 48 hours befor e t h e procedure, and were a l l o w e d t o d r i n k ad f i b i h m .
Tobacco,
c o f f e e , tea, a l c o h o l i c beverages, bananas, oranges, cheese, v a n i l l a , cocoa o r any drugs were p r o h i b i t e d f o r a t l e a s t 12h b e f o r e t h e p r o cedure.
Meals were served a t 8:15h,
c o l l e c t e d e v e r y 4 hours ( a t 12:30h,
12:15h and 18:OOh. 16:30h,
20:30h,
U r i n e was
0:30h, 4:30h and
8:30h) from 10 s u b j e c t s and e v e r y 4 hours ( a t 12:30h,
16:30h, 20:30h
and 0:30h) and once f o r t h e n i g h t p e r i o d ( a t 8:30h) from 3 s u b j e c t s . U r i n e samples were c o l l e c t e d i n f l a s k s c o n t a i n i n g 10 m l o f concentrated p e r c h l o r i c a c i d o r 0.5% sodium m e t a b i s u l f i t e , and t h e n s t o r e d f r o z e n a t -2OOC u n t i l assayed.
U r i n a r y dopamine, n o r e p i n e -
p h r i n e and e p i n e p h r i n e were determined by two f l u o r o m e t r i c methods (17,181 g i v i n g h i g h l y r e p r o d u c i b l e values.
The catecholamines o f
FAUCHEUX ET AL.
260
3 subjects were also determined by a modified isotopic method of
Coyle and Henry (19) using S-adenosyl-L-methionine (methyl 3H) as a methyl donor. The inter-assay coefficient of correlation with the fluorometric method (18) was 0.97 (p < 0.001) for 8 samples. HVA was determined by the method of Sato (ZO), sodium and potass um by flame photometry and creatinine by the method of Cooper and Biggs (21). Endocr Res Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
Analyses of variance for single factor experiments having repeated measurements of the same quantities were performed on each excreted substance. The following data were calculated individually for each substance:
a) mean excretion per hour for each urine collection period
(XI; b ) mean excretion per hour during the 24h cycle
(2 24h);
c) percentage o f the mean excretion value relative to the 24h cycle
X
X 100 ;
(r m i )
d) amplitude (A) expressed as the difference between the maximum and the minimum of the excretion values; e) relative variation, expressed as a percentage of the amplitude of the circadian oscillation relative to the mean excretion value over the 24h cycle
A
(f
X 100
24h
)
;
f) times of the maximum and minimum of the excretion values calculated in hours corresponding to the mid period of the urine collection including the maximum or the minimum.
DIURNAL RHYTHM OF CATECHOLAMINES
261
RESULTS The data in Table I show a circadian v a r i a t i o n f o r a l l the studied parameters, w i t h a nocturnal minimum between 0:30h and 8:30h (during t h e period of s l e e p ) and a maximum between 12:30h and A s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e between the day and
20:30h.
n i g h t excretions was not c l e a r l y demonstrated f o r c r e a t i n i n e , NE
o r HVA ( f o r t h i s l a s t parameter, we analysed only 7 of t h e 13 subThe values of HVA from t h e 8:30h t o 12:30h period were how-
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jects).
ever s i g n i f i c a n t l y ( p < 0.02) higher than those during t h e night. Table I1 i l l u s t r a t e s t h a t HVA and E excretions had t h e highe s t r e l a t i v e v a r i a t i o n s during t h e i r respective circadian rhythms. In a d d i t i o n , HVA had t h e highest mean e x c r e t i o n , and i t s amplitude was c l o s e t o t h a t of the urinary volume.
The maxima of a l l measu-
red parameters appeared i n t h e afternoon between 14:30h and 18:OOh ( c l o s e t o the highest excretion periods of Table I in which t h e data a r e expressed as absolute v a l u e s ) .
The minima of catecholami-
ne excretion were found i n t h e f i r s t half of the night f o r D A Y N E and E , and i n t h e e a r l y morning f o r HVA.
The time of occurrence
of the lowest values of urine volumes, urinary c r e a t i n i n e and urinary e l e c t r o l y t e s were comparable, approximatly 4:OOh t o 5:OOh i n the morning. ed
The data of Table I1 a r e emphasized by t h e i r b e i n g express-
as the percentage of t h e mean of t h e 24h e x c r e t i o n , i n Fig. 1
f o r t h e catecholamines and i n Fig. 2 f o r t h e o t h e r parameters.
When
so presented t h e d i f f e r e n c e s between t h e nocturnal urinary excretion and a t l e a s t one o r several d a i l y c o l l e c t i o n periods became s t a t i s t i c a l l y s i g n i f i c a n t f o r a l l parameters.
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The d i f f e r e n c e between t h e maximum and t h e minimum o f t h e e x c r e t i o n . The expression o f t h e amplitude as t h e percentage o f t h e mean v a l u e o f t h e e x c r e t i o n over t h e 24h c y c l e . Expressed i n hours and t e n t h o f hours from m i d n i g h t ( 0 ) t o 24.
4.2 f 0.8
(mEq/h)
162
6.0 f 0.6
3.7 f 0.2
POTASSIUM
4.5 f 1 . 0
16.7 & 1.0 14.5 & 0.5
126
11.1 f 1 . 2
8.8 f 0 . 9
(mEq/h)
48
2.9
SODIUM
5.4 f 1.1 5.6 f 1.4
17.3 f 1.2 16.0 & 1.2
138
240 f 46 32.0 f 5.4
174 f 17 66.8
(ml/h) (mg/ h )
CREATIN I NE
DIURESIS
2.3 & 1.5
4.0 f 1.6 15.7 & 1.3
84 143
15.4 +_ 1.3
1.51 f 0.24 0.53 f 0.08
1.79 +_ 0.19 0.37 f 0.05
(us/ h )
3 . 0 f 1.4 8.5 f 2.0
16.7 f 1 . 3 17.9 f 1 . 6
80 156
EPINEPHRINE
f 87
10.5 f 2.6 212
13.2 f 1 . 6 136 f 42
(m/h)
HVA (!N/h) NOREPINEPHRINE (pg/h)
DOPAMI NE
Minimum
of t h e
mean & SEM
mean f SEM
mean & SEM
Timet Maximum mean & SEM
%
Amp1 itude*
Re1 a t i ve V a r i a t i o n * *
CHARACTERISTICS OF THE C I R C A D I A N V A R I A T I O N S .
Mean E x c r e t i o n
TABLE 11:
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264
FAUCHEUX ET AL.
FIGURE 1 Urinary excretion of dopamine, homovanill ic acid (HVA), norepinephrine, and epinephrine expressed as the percentage change from the mean of the 24 hours excretion. The shaded area represents the period of sleep. The night periods are expressed separately (open bars, darker shaded area respectively) for two four hour collection periods (0:304:30 and 4:30 to 8:30) for 10 subjects and for one 8 hour collection period (0:30-8:30) for all 13 subjects (except for HVA which has been determined in the two four hour collection periods only). The final 8:30-12:30 period is repeated for comparison. Statistical significance of variance analysis versus the night urine collection (0:308:30) *p < 0.05 and ** for p < 0.01.
A significant positive correlation between the urinary values
of DA and NE (r = 0.365, p < 0.01) and between DA and E (r = 0.367,
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DIURNAL RHYTHM OF CATECHOLAMINES
265
FIGURE 2
U r i n a r y volume, c r e a t i n i n e , sodium and potassium e x c r e t i o n expressed i n t h e same way as on F i g u r e 1.
p < 0.01) was observed.
No c o r r e l a t i o n was found between DA and HVA
d e s p i t e t h e i r c l o s e m e t a b o l i c r e l a t i o n s h i p and t h e i r synchronism d u r i n g a p a r t o f t h e 24h c y c l e .
FAUCHEUX ET AL.
266
U r i n a r y sodium e x c r e t i o n p o s i t i v e l y c o r r e l a t e d w i t h u r i n a r y E e x c r e t i o n ( r = 0.327,
p < 0.02) b u t n o t w i t h u r i n a r y NE o r DA.
U r i n a r y NE was c o r r e l a t e d t o u r i n a r y c r e a t i n i n e e x c r e t i o n (r = 0.281, p < 0.05) as w e l l as u r i n a r y E e x c r e t i o n ( r = 0.408,
p < 0.005) b u t
no c o r r e l a t i o n was observed between u r i n a r y DA, HVA and c r e a t i n i n e . None o f t h e u r i n a r y catecholamines had any s i g n i f i c a n t c o r r e l a t i o n w i t h t h e u r i n e volume.
However, t h e r e was a s i g n i f i c a n t c o r r e l a t i o n
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between u r i n a r y volume and sodium e x c r e t i o n
( r = 0.269, p < 0.05)
b u t n o t between u r i n a r y volume and potassium e x c r e t i o n .
DISCUSSION A l l s t u d i e d parameters have shown a minimum d u r i n g t h e n i g h t , when b o d i l y a c t i v i t i e s and p h y s i o l o g i c a l f u n c t i o n s a r e reduced and s i g n i f i c a n t l y d i f f e r e n t from those d u r i n g t h e waking periods.
Over
the whole d i u r n a l cycle, t h e e x c r e t i o n p a t t e r n s changed i n many cases continuously from one c o l l e c t i o n p e r i o d t o t h e n e x t one, between the minimum and t h e maximum. The d i u r n a l rhythm o f various catecholamines seems t o be mor e o r l e s s synchronized; t h i s i s t r u e f o r NE and
E
b u t does n o t
apply t o DA and HVA f o r which some subjects had a peak i n t h e beginn i n g o f ' t h e afternoon and others j u s t before t h e p e r i o d of sleep. Such f l u c t u a t i o n s have a l s o been found i n another group o f young males s t u d i e d f o r several consecutive days f o r which DA v a r i e d from one day t o the o t h e r ( 3 ) . Times o f maxima and minima f o r catecholamine e x c r e t i o n correspond c l o s e l y t o those already r e p o r t e d i n t h e l i t e r a t u r e (3,4,
DIURNAL RHYTHM OF CATECHOLAMINES 7,8,10,12).
267
I n c o n t r a s t t o t h e f i n d i n g of Wiser e t a l . ( 3 ) i n
which t h e minimum o f DA appeared around 3:OOh we observed i t b e t ween 4:OOh and 8;OOh.
Contrary t o other authors ( 5 , 6 ) our r e s u l t s
demonstrate a s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e ( p ween t h e n i g h t and t h e f o l l o w i n g day p e r i o d .
CIRCADIAN VARIATIONS OF THE URINARY EXCRETION OF CATECHOLAMINES A N D ELECTROLYTES?
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6. Faucheux*, 0. Kuchel, J.L. Cuche**, F.H. Messerli***, N.T. B U U , A. Barbeau and J . Genest. Clinical Research I n s t i t u t e of Montreal, Laboratory o f the Sympathetic Nervous System, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7. *Present address: 6. Faucheux,Ph.D., I.N.S.E.R.M. -U-118, 29 rue Wilhem, Paris 75016, FRANCE. **Present address: J.L. Cuche,M.D., I.N.S.E.R.M. -U-27, Centre Medico-Chirurgical Foch, Suresnes 92150, FRANCE. ***Present address: F.H. Messerli,M.D., Medical P o l i c l i n i c , University Medical School, Bern, SWITZERLAND. ABSTRACT
Concomitant measurements of c i r c a d i a n v a r i a t i o n s i n t h e urinary excretion of dopamine ( D A ) , homovanillic acid ( H V A ) , norepinephrine ( N E ) , epinephrine ( E ) as well as of c r e a t i n i n e , sodium and potassium under controlled d i e t a r y conditions d u r i n g r e l a t i v e physical and emotional r e s t i n 13 volunteers have shown t h a t maximum excretion of a l l these substances occurred in t h e afternoon period between 14:30h and 18:00h, and minimum excretion in t h e morning between 4:OOh and 5:OOh. The changes were i n some cases progressive from one c o l l e c t i o n period t o t h e o t h e r , and synchronized f o r N E and E . DA and HVA excretions f l u c t u a t e d from s u b j e c t t o s u b j e c t . Excretory rhythms of sodium and potassium were found t o be s i m i l a r t o those of t h e catecholamines. This can be explained by diurnal changes in renal blood flow and d i f f e r e n t renal excretory mechanisms of catecholamines. None of t h e catecholamines correl a t e d with t h e urinary volume b u t urinary NE and E p o s i t i v e l y corr e l a t e d with urinary c r e a t i n i n e , urinary NE and E w i t h urinary DA and urinary sodium w i t h urinary E . There a r e some common p a t t e r n s in t h e diurnal rhythms o f catecholamines and e l e c t r o l y t e s b u t t h e i r i n t e r r e l a t i o n s h i p i s d i f f e rent f o r individual catecholamines.
t Reprints requests:
Otto Kuchel, M.D., Montreal , Quebec, Canada H2W 1R7.
110 Pine Avenue West,
257 Copyright 0 1976 by Marcel Dekker, Inc. All Rights Reserved Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher.
FAUCHEUX ET AL.
258
Circadian variations have been reported f or the catecholamines dopamine (DA) (1-4) (and i t s main metabolite homovanillic acid (HVA) (4-6) ) , norepinephrine (NE)
, and epinephrine
( E ) (4,7-12)
,
nonetanephrine and vanillylmandelic acid (VMA) (13) as well as for urinary electrolytes (14).
Different results have been obtained in
these studies , however, probably because of differ ent protocols and
Endocr Res Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
experimental methods, such as dif fer ent durations of urine collections and changes in body position.
Among the many variables, the
relationship between e le c t rol yte and catecholamine excretion i s of special i n t e r e s t since a relationship between the urinary excretion of NE and particularly OA and sodium has
been demonstrated during
upright posture (15) and sodium-load-induced volume expansion ( 1 6 ) . I t i s therefore important t o study concomitantly in the same subj e c t the excretion of catecholamines and electrolytes during bed r e s t , eliminating a l l the e ffe c ts of upright posture and of str essful stimuli and under controlled dietary conditions.
The main ob-
j e ct i ve of t h i s study was t o determine the excretion patterns of three catecholamines (DA, NE, E ) , one of t h e i r metabolites ( H V A ) , and urinary electrolytes (sodium and potassium) and t h e i r interrelationships.
Collection periods were relatively shorter than in
most previous studies. MATERIALS AND METHODS
Thirteen healthy volunteers ( 2 females and 11 males) between the age of 19 and 53 years (26 tory were chosen f o r the study.
*
2 years) with a normal medical his-
Complete physical examination re-
259
DIURNAL RHYTHM OF CATECHOLAMINES
vealed no a b n o r m a l i t i e s , t h e b l o o d pressure was always under 135/90 mmHg and t h e usual l a b o r a t o r y b l o o d and u r i n e t e s t s were w i t h i n n o r mal l i m i t s .
Women were i n v e s t i g a t e d i n t h e f i r s t h a l f o f t h e i r
menstrual c y c l e s and none o f them r e c e i v e d o r a l c o n t r a c e p t i v e s f o r a t l e a s t 3 months p r i o r t o t h e study. The s u b j e c t s were a d m i t t e d t h e evening p r i o r t o t h e day of t h e study i n t o a q u i e t a i r c o n d i t i o n e d p h y s i o l o g y room w i t h a s t a b l e Endocr Res Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
a i r temperature (22OC), and were asked t o a v o i d any undue s t r e s s e s . They were asked t o s t a y i n bed d u r i n g t h e whole 24h i n v e s t i g a t i o n t o a v o i d any posture-induced v a r i a t i o n s .
They s l e p t between 23:OOh
and 8:OOh and were awake d u r i n g t h e day-time,
spending t h e i r t i m e
r e a d i n g and watching t e l e v i s i o n . The s u b j e c t s i n g e s t e d a d a i l y d i e t c o n t a i n i n g 135 mEq o f sodium and 90 mEq o f potassium, which had been s t a r t e d 48 hours befor e t h e procedure, and were a l l o w e d t o d r i n k ad f i b i h m .
Tobacco,
c o f f e e , tea, a l c o h o l i c beverages, bananas, oranges, cheese, v a n i l l a , cocoa o r any drugs were p r o h i b i t e d f o r a t l e a s t 12h b e f o r e t h e p r o cedure.
Meals were served a t 8:15h,
c o l l e c t e d e v e r y 4 hours ( a t 12:30h,
12:15h and 18:OOh. 16:30h,
20:30h,
U r i n e was
0:30h, 4:30h and
8:30h) from 10 s u b j e c t s and e v e r y 4 hours ( a t 12:30h,
16:30h, 20:30h
and 0:30h) and once f o r t h e n i g h t p e r i o d ( a t 8:30h) from 3 s u b j e c t s . U r i n e samples were c o l l e c t e d i n f l a s k s c o n t a i n i n g 10 m l o f concentrated p e r c h l o r i c a c i d o r 0.5% sodium m e t a b i s u l f i t e , and t h e n s t o r e d f r o z e n a t -2OOC u n t i l assayed.
U r i n a r y dopamine, n o r e p i n e -
p h r i n e and e p i n e p h r i n e were determined by two f l u o r o m e t r i c methods (17,181 g i v i n g h i g h l y r e p r o d u c i b l e values.
The catecholamines o f
FAUCHEUX ET AL.
260
3 subjects were also determined by a modified isotopic method of
Coyle and Henry (19) using S-adenosyl-L-methionine (methyl 3H) as a methyl donor. The inter-assay coefficient of correlation with the fluorometric method (18) was 0.97 (p < 0.001) for 8 samples. HVA was determined by the method of Sato (ZO), sodium and potass um by flame photometry and creatinine by the method of Cooper and Biggs (21). Endocr Res Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
Analyses of variance for single factor experiments having repeated measurements of the same quantities were performed on each excreted substance. The following data were calculated individually for each substance:
a) mean excretion per hour for each urine collection period
(XI; b ) mean excretion per hour during the 24h cycle
(2 24h);
c) percentage o f the mean excretion value relative to the 24h cycle
X
X 100 ;
(r m i )
d) amplitude (A) expressed as the difference between the maximum and the minimum of the excretion values; e) relative variation, expressed as a percentage of the amplitude of the circadian oscillation relative to the mean excretion value over the 24h cycle
A
(f
X 100
24h
)
;
f) times of the maximum and minimum of the excretion values calculated in hours corresponding to the mid period of the urine collection including the maximum or the minimum.
DIURNAL RHYTHM OF CATECHOLAMINES
261
RESULTS The data in Table I show a circadian v a r i a t i o n f o r a l l the studied parameters, w i t h a nocturnal minimum between 0:30h and 8:30h (during t h e period of s l e e p ) and a maximum between 12:30h and A s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e between the day and
20:30h.
n i g h t excretions was not c l e a r l y demonstrated f o r c r e a t i n i n e , NE
o r HVA ( f o r t h i s l a s t parameter, we analysed only 7 of t h e 13 subThe values of HVA from t h e 8:30h t o 12:30h period were how-
Endocr Res Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
jects).
ever s i g n i f i c a n t l y ( p < 0.02) higher than those during t h e night. Table I1 i l l u s t r a t e s t h a t HVA and E excretions had t h e highe s t r e l a t i v e v a r i a t i o n s during t h e i r respective circadian rhythms. In a d d i t i o n , HVA had t h e highest mean e x c r e t i o n , and i t s amplitude was c l o s e t o t h a t of the urinary volume.
The maxima of a l l measu-
red parameters appeared i n t h e afternoon between 14:30h and 18:OOh ( c l o s e t o the highest excretion periods of Table I in which t h e data a r e expressed as absolute v a l u e s ) .
The minima of catecholami-
ne excretion were found i n t h e f i r s t half of the night f o r D A Y N E and E , and i n t h e e a r l y morning f o r HVA.
The time of occurrence
of the lowest values of urine volumes, urinary c r e a t i n i n e and urinary e l e c t r o l y t e s were comparable, approximatly 4:OOh t o 5:OOh i n the morning. ed
The data of Table I1 a r e emphasized by t h e i r b e i n g express-
as the percentage of t h e mean of t h e 24h e x c r e t i o n , i n Fig. 1
f o r t h e catecholamines and i n Fig. 2 f o r t h e o t h e r parameters.
When
so presented t h e d i f f e r e n c e s between t h e nocturnal urinary excretion and a t l e a s t one o r several d a i l y c o l l e c t i o n periods became s t a t i s t i c a l l y s i g n i f i c a n t f o r a l l parameters.
*o
w
.. y
m
-
+I
0
..
m
*o m ..
Endocr Res Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
6
O N
0
+I
+I
+I
+I
+I
+I
m
7
m
h
7
-
0 N
.*
O
N
m *.
w -
..
d Ln 0
m
7
W
m
N
N
0
0
0 N
0
+I
+I
+I
+I
+I
m
Ln
0
m
-
N W
d
N
N
0
m
m
..
N -
0
m
..
-
N
m
0 0
+I m 7
0
W N
7
0
0
10
W
W
7
0
d d
i-l
+I
+I
+I
+I
+I
+I
W
Ln
Ln
m
0
P-
7
N N
h W
0
m
m
-
m
7
d
Ln
7
09 0
+I
+I
+I
+I
w m
d: m
d
cr
-
7
Ln
Ln
7
+I
+I
h
7
ID
N
Ln
m
h
7
7 d
+I 0 W N
o m
+I
0
m
.. 3 mh7
0
h W
m
7
N d 0
+I
+I
7
m
0
0 d
7
Lo
N
N
0
Ln
m
h N
m 0
0
7
0
0
+I
+I
+I
+I
0
Ln 0
d
0
7
h
7
-
0 h
m
7
m
7
d
7
0
+I
+I
+I
m +I
N
h
Ln
0
m
m
7
W
m
0
+I
Ln
h
d: 0
a2
N
N
7
d
c
6
Ln
0
7
0
m w
d ID
0
7
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0
m
0
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m
..
-
In
m
.. 0
W h
7
0
m
0
+I Ln
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w
m
N
+I W
m
0
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m
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0
7 +I
0
+I 0
N
0
W
-
m
+I Ln
m 0
0
N
..
+I 0
7
N
7
0
0
Ln
w
m
v
m
N
0
..
Ln
m
-
d
0
W
Ln
m
m
0
m
d h
d
N
0 W
0
7
m
0
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+I
+I
Lo
0
N
0
Y
h
Lr v
-0
0 .r
h h
L c 0 1 1 Q
-
s0 . 5
h
c \
E?
v
c 1 0W
E
v
h
c 1 W 0-
E v
h
h
1
\
c
m 7
v
c cn
7
v
h
c m
1
7
v
.r
CI V
w
w
h
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0 0
h
W v)
-
L v )
m
S
u
E
.r
3
3
0
L
z Y
7
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z z
= x I
Y
I
E cf
a
5-
z
0
U
Y
n
I4 -:
u
v) 0
a 0
rc
> 4: x
W
W
a
v) v)
9
5 cf
lx
I
+ b.4
II s
a
W lx 0 z
r
W
z Y
a W
t
* **
The d i f f e r e n c e between t h e maximum and t h e minimum o f t h e e x c r e t i o n . The expression o f t h e amplitude as t h e percentage o f t h e mean v a l u e o f t h e e x c r e t i o n over t h e 24h c y c l e . Expressed i n hours and t e n t h o f hours from m i d n i g h t ( 0 ) t o 24.
4.2 f 0.8
(mEq/h)
162
6.0 f 0.6
3.7 f 0.2
POTASSIUM
4.5 f 1 . 0
16.7 & 1.0 14.5 & 0.5
126
11.1 f 1 . 2
8.8 f 0 . 9
(mEq/h)
48
2.9
SODIUM
5.4 f 1.1 5.6 f 1.4
17.3 f 1.2 16.0 & 1.2
138
240 f 46 32.0 f 5.4
174 f 17 66.8
(ml/h) (mg/ h )
CREATIN I NE
DIURESIS
2.3 & 1.5
4.0 f 1.6 15.7 & 1.3
84 143
15.4 +_ 1.3
1.51 f 0.24 0.53 f 0.08
1.79 +_ 0.19 0.37 f 0.05
(us/ h )
3 . 0 f 1.4 8.5 f 2.0
16.7 f 1 . 3 17.9 f 1 . 6
80 156
EPINEPHRINE
f 87
10.5 f 2.6 212
13.2 f 1 . 6 136 f 42
(m/h)
HVA (!N/h) NOREPINEPHRINE (pg/h)
DOPAMI NE
Minimum
of t h e
mean & SEM
mean f SEM
mean & SEM
Timet Maximum mean & SEM
%
Amp1 itude*
Re1 a t i ve V a r i a t i o n * *
CHARACTERISTICS OF THE C I R C A D I A N V A R I A T I O N S .
Mean E x c r e t i o n
TABLE 11:
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Endocr Res Downloaded from informahealthcare.com by University of Otago on 01/07/15 For personal use only.
264
FAUCHEUX ET AL.
FIGURE 1 Urinary excretion of dopamine, homovanill ic acid (HVA), norepinephrine, and epinephrine expressed as the percentage change from the mean of the 24 hours excretion. The shaded area represents the period of sleep. The night periods are expressed separately (open bars, darker shaded area respectively) for two four hour collection periods (0:304:30 and 4:30 to 8:30) for 10 subjects and for one 8 hour collection period (0:30-8:30) for all 13 subjects (except for HVA which has been determined in the two four hour collection periods only). The final 8:30-12:30 period is repeated for comparison. Statistical significance of variance analysis versus the night urine collection (0:308:30) *p < 0.05 and ** for p < 0.01.
A significant positive correlation between the urinary values
of DA and NE (r = 0.365, p < 0.01) and between DA and E (r = 0.367,
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DIURNAL RHYTHM OF CATECHOLAMINES
265
FIGURE 2
U r i n a r y volume, c r e a t i n i n e , sodium and potassium e x c r e t i o n expressed i n t h e same way as on F i g u r e 1.
p < 0.01) was observed.
No c o r r e l a t i o n was found between DA and HVA
d e s p i t e t h e i r c l o s e m e t a b o l i c r e l a t i o n s h i p and t h e i r synchronism d u r i n g a p a r t o f t h e 24h c y c l e .
FAUCHEUX ET AL.
266
U r i n a r y sodium e x c r e t i o n p o s i t i v e l y c o r r e l a t e d w i t h u r i n a r y E e x c r e t i o n ( r = 0.327,
p < 0.02) b u t n o t w i t h u r i n a r y NE o r DA.
U r i n a r y NE was c o r r e l a t e d t o u r i n a r y c r e a t i n i n e e x c r e t i o n (r = 0.281, p < 0.05) as w e l l as u r i n a r y E e x c r e t i o n ( r = 0.408,
p < 0.005) b u t
no c o r r e l a t i o n was observed between u r i n a r y DA, HVA and c r e a t i n i n e . None o f t h e u r i n a r y catecholamines had any s i g n i f i c a n t c o r r e l a t i o n w i t h t h e u r i n e volume.
However, t h e r e was a s i g n i f i c a n t c o r r e l a t i o n
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between u r i n a r y volume and sodium e x c r e t i o n
( r = 0.269, p < 0.05)
b u t n o t between u r i n a r y volume and potassium e x c r e t i o n .
DISCUSSION A l l s t u d i e d parameters have shown a minimum d u r i n g t h e n i g h t , when b o d i l y a c t i v i t i e s and p h y s i o l o g i c a l f u n c t i o n s a r e reduced and s i g n i f i c a n t l y d i f f e r e n t from those d u r i n g t h e waking periods.
Over
the whole d i u r n a l cycle, t h e e x c r e t i o n p a t t e r n s changed i n many cases continuously from one c o l l e c t i o n p e r i o d t o t h e n e x t one, between the minimum and t h e maximum. The d i u r n a l rhythm o f various catecholamines seems t o be mor e o r l e s s synchronized; t h i s i s t r u e f o r NE and
E
b u t does n o t
apply t o DA and HVA f o r which some subjects had a peak i n t h e beginn i n g o f ' t h e afternoon and others j u s t before t h e p e r i o d of sleep. Such f l u c t u a t i o n s have a l s o been found i n another group o f young males s t u d i e d f o r several consecutive days f o r which DA v a r i e d from one day t o the o t h e r ( 3 ) . Times o f maxima and minima f o r catecholamine e x c r e t i o n correspond c l o s e l y t o those already r e p o r t e d i n t h e l i t e r a t u r e (3,4,
DIURNAL RHYTHM OF CATECHOLAMINES 7,8,10,12).
267
I n c o n t r a s t t o t h e f i n d i n g of Wiser e t a l . ( 3 ) i n
which t h e minimum o f DA appeared around 3:OOh we observed i t b e t ween 4:OOh and 8;OOh.
Contrary t o other authors ( 5 , 6 ) our r e s u l t s
demonstrate a s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e ( p ween t h e n i g h t and t h e f o l l o w i n g day p e r i o d .
