Urine Volume and Osmolality Changes During Dreaming Sleep in Man*

Transcription

1 X Urine Volume and Osmolality Changes During Dreaming Sleep in Man* A. J. Mandell, 6. Chaffey, P. Sri 11, M. P. Mandell, J. Rodnick, R. T. Rubin and R. Sheff Biochemical Correlates Laboratory Departments of Psychiatry and Urology, U.C.L.A. Center for the Health Sciences and the Brentwood Veterans Administration Hospital Los Angeles 2k, California OS-HOLUr'Tl-CBiBGE'r EU5IKG IBZ*BIBG SIIEf IK {CalifcrtJa Univ.) 6 c 00/52' ^Supported in part by NASA Grant NsG under the aegis of The Space Biology Laboratory; drain Research Institute, U.C.L.A. Health Science Center.

2 Urine Volume and Osmolality Changes During Dreaming Sleep in Man Abstract: REMS (dreaming sleep) epochs were found to be consistently correlated with a biphasic change in urine volume and osmolality in catheterized human subjects. A marked decrease in volume and increase in osmolality was followed by a hypotonic diuresis. A recent study (1) demonstrating autonomic and respiratory changes associated with the rapid eye movement state (REMS) during sleep stimulated us to attempt to elucidate neuroendocrine correlates associated with this state, because subcortical systems influencing peripheral physiological events have been shown to act through the pituitary-adrenal axis (2). We therefore instituted a study of urinary volume, osmolality, creatinine concentration, and steroid and catechol amine metabolites serially collected during allnight electrophysiologically monitored sleep in man. The following is a report of a consistent urinary volume correlate of the REMS and some findings which suggest the mechanism involved. Seven urinary catheter-adapted, male urology patients, ages ^5-7^, with normal renal function tests were studied for a total of eleven nights using conventional EEC, EMG, and EOG recordings in a sound-attenuated, darkened room (3). The urinary catheters were led from the room into a volume-regulated fraction collector which permitted continuous collection of urine samples of uniform volume, the volumes being measured accurately following collection. The electrical recordings were scored for REMS without knowledge of the data from the urine studies, using the criteria of Dement (k). The time of onset and length of the rapid eye movement periods were carefully determined. The filling of each tube in the fraction collector was timelocked to the electrophysiological data by an event recorder fed into an

3 -2- amplifier of one channel of the electroencephalograph. Urinary creatinine was determined by the method of Jaffe. The osmolality of the urine samples was measured by freezing point depression, using an Advanced Osmometer. AJ1 forty-one REMS epochs recorded during the 11 nights were associated with a biphasic urine volume response of varying magnitude (Fig. 1 and Fig. 2). With some variability in latency, but usually within two minutes of the onset of the REMS, there was marked decrease in urine drop rate from the catheter into the fraction collector. This decrease was followed by an increase of even greater magnitude following the end of the REMS. These changes are smoothed out somewhat in Fig. I and 2 because of overlap of antidiuretic and diuretic effects in the serial, constant volume aliquots. One possible explanation for this change was an autonomically mediated mechanical factor such as alteration of bladder tone or compression of the catheter lumen by penile erections shown to accompany the REMS (5). However as shown in Fig. 1 and 2, reciprocal changes in urine osmolality and creatinine are associated with the volumetric shifts; mechanical storage or blockage effects in the urinary collecting system would not alter the composition of the urine in such a fashion. This suggested that the change in urine flow associated with the REMS was a central nervous system-induced change in renal function. Pitts (6) concludes that except for renal disease states or extremely marked volemic changes leading to circulatory embarrassment, urine flow changes in man are for the most part effected by changes in water reabsorption, not by changes in filtration rate. Two neuroendocrine mechanisms affecting water and solute reabsorption by the kidney tubule, which could be triggered by shifts in CNS events, are the release of aldosterone from the

4 -3- adrenal with a resulting increase in sodium reabsorption and an isosmotic decrease in volume, and the release of ADH-like substances from the posterior pituitary with a hypertonic volume reduction. Our data show a consistent inverse change in urine osmolality with changes in volume, indicating an alteration primarily in the water rather than in the sodium reabsorptive mechanism. However, before concluding that the urine volume changes were secondary to ADH release, some indication of the constancy of glomerular filtration rate is necessary. Since these studies were done during sleep and were of repeated measurements, the use of the more accurate reflection of GFR, inulin clearance, was not possible. Though endogenous creatinine clearance in man has high individual variability and in addition to being filtered is partially secreted by the tubule (and therefore its clearance exaggerates GFR), it is used by some groups (7) as a rough measure of GFR. Since plasma creatinine levels did not change significantly from evening to morning in our subjects, the expression for the change in creatinine clearance Uv' Uc' - Uv Uc becomes Uv 1 Uc 1 - Uv Uc. Pc 1 PC Since Uv varies inversely with Uc (See Figs. 1 and 2) Uv Uc - k and r+* Uv 1 Uc 1 - Uv Uc = 0. Therefore, although this is a rough approximation because of small collection periods and collection periods which include both low and high urine output, it appears that the volume and osmolality changes are independent of changes in glomerular filtration. This is what might be expected in view of the reported stability of GFR in healthy man (8). It is possible that the ADH-like initial effect may be secondary to cardiorespiratory irregularities (I) associated with the REMS and consequent ADH release via brain stem vasomotor reflexes (9). Changes of pressure in both the left atrium and the carotid baroreceptors have been

5 -itreported to influence ADH release as part of the blood volume regulatory system. However the quite short latency and regularity of appearance of the hypertonic decrease in urine flow during the first two minutes of the REMS combined with the irregular time of appearance of cardiovascular irregularities (10) makes this explanation unlikely. The volume and osmolality changes are more likely to be a concomitant of central nervous system changes associated with the REMS. Evidence has been presented by many workers (11) that the REMS may be a special kind of "arousal" with many of its central and peripheral manifestations resembling more an awake than a sleeping state. We have recently reviewed a number of studies indicating that various kinds of emotional arousal states in man are associated with decreases in urine volume (12) probably secondary to ADH release. This present investigation demonstrates that short periods of lying awake in the middle of the night (not the early diuretic phenomena associated with lying down and going to sleep) are associated with the same biphasic response of urine volume and osmolality that is seen in the REMS (Fig. 2). Brain stem and limbic "activation" associated with the REMS (1) may be transmitted to the hypothalamic nuclei involved with ADH control via established pathways (2, 13). A. J. Mandell, 3. Chaffey, P. Brill, M. P. Mandell, J. Rodnick, R. T. Rubin and R. Sheff Biochemical Correlates Laboratory Departments of Psychiatry and Urology, U.C.L.A. Center for the Health Sciences and the Brentwood VeteransAdministration Hospital Los Angeles 2k, California

6 References and Notes 1. Snyder, F. Am. J. Psychiat., Oct (In press). 2. Green, J. D. Physiol. Rev. 44:461, 1964; Nauta, W. J. W. in Nalbandov (Ed.) Advances in Neuroendocrinology. Univ Press, Urbana, 1963; Mandell, A. J., Chapman, L. F., Rand, R. W. and Walter, R. D., Science 139:1212, Jacobson, A., Kales, A., Zweizig, J. R., and Kales, J. Am. J. EEG Technol. 5:5, Dement, W. The Physiology of Dreaming (Ph.D. Thesis), Univ. of Chicago, Fisher, C., Gross, J., Zuch, J. Arch. Gen. Psychiat. 12:29, Pitts, R. F. Physiology of the Kidney and Body Fluids. Year 8ook, Chicago, 111., 1963, p Mattar, G., Barnett, H. L., McNamara, H. and Lauson, H. D. J. Clin. Invest. 31:938, Strauss, M. D. Arch. Int. Med. 103: 489, Parrel 1, G. and Taylor, A. N. Ann. Rev. Physiol. 24:471, Snyder, F. Science 142:1313, Winters, W. C. EEG and Clin. Neurophysiol. 17:234, Mandell, A. J. Am. Heart J. 65:572, Supported in part by NASA Grant NsG under the aegis of The Space Biology Laboratory; Brain Research Institute, U.C.L.A. Health Science Center.

7 .k.-', >-:m<-.;-..! ;> '. '.HOURS AFTER 5 FALLING 7, ASLEEP : f.. '. ^ Fig. I. Simultaneous plot of volume, osmolarity (osmolality), creatinine concentration and REMS epochs during a typical night's sleep. The hyptonlc cturesls associated with,the first hour or so of recumbency and sleep.has been omitted. t~ '' '*' ; V ', '/ " " ' *?,'! _' : -'.A-" ; " ". Y--" : Y--r v >:

8 N r o i i_ 500-.= i.oo i u at "5 E o 450- E o> Greatin ine o Osmolorify u o ho. 40 UJ T o '* Volume J REMS I AWAKE I '/ 3 MINUTE INTERVALS Fig. 2. A comparison of the changes in some urine variables during a REMS and a middle of the night arousal period; note the similarity of the directions of change.