Sleep, 14(1):83-86 © 1991 American Sleep Disorders Association

Short Notes

Atrial Natriuretic Peptide and Catecholamines in Obstructive Sleep Apnea Syndrome

Institute of Neurology, University of Bologna, Bologna, Italy

Summary: Nocturnal polyuria with repeated micturitions during the night is a clinically evident feature of obstructive sleep apnea syndrome (OSAS). These effects are reversed by continuous positive airway pressure (CPAP). There is some evidence that atrial natriuretic peptide (ANP) and catecholaminergic activity may be implicated in the pathogenesis of these symptoms. We studied these biochemical parameters in six patients with severe OSAS during two nights: the first (basal) in their normal conditions and the second during CPAP treatment. CPAP treatment reversed apnea episodes in all our patients. A significant (p < 0.035) reduction of nocturnal urine volume (from 902 ± 297 to 447 ± 130 ml; mean ± SD), sodium excretion (from 150 ± 33 to 89 ± 35 mEq/12 h), noradrenaline excretion (from 95 ± 101 to 52 ± 16 J.Lglg creatinine), noradrenaline plasma concentrations (from 325 ± 96 to 259 ± 75 pglml), ANP plasma concentrations (from 35 ± 20 to 19 ± 5 pglml) was observed during the night under CPAP application. These data suggest that in OSAS patients the high ANP plasma concentration is responsible for the observed elevated diuresis and sodium excretion. These effects are rapidly reversible, as they are reversed during the first CPAP treated night. Key Words: Catecholamines-Atrial natriuretic factor-Sleep apnea-Continuous positive airway pressure.

Patients with obstructive sleep apnea syndrome (OSAS) frequently complain of marked nocturnal diuresis (1,2), which subsides after apnea reversal by nasal continuous positive airway pressure (CPAP) treatment (3,4). There is some evidence that changes in catecholaminergic activity (5,6) and increased release of atrial natriuretic peptide (ANP) (4,7), which seem to occur during disturbed sleep in untreated OSAS patients, may be involved in the pathogenesis of these urinary symptoms. Moreover, there is evidence that ANP interacts with noradrenergic blood pressure control mechanisms in man (8), and modifications of these compounds may, in some way, be implicated in the development of hypertension in OSAS patients. However, to our knowledge, no study has measured plasma concentrations of ANP and catecholamines together during sleep in the same patient before and during one night of effective CPAP treatment. We investigated the within-subject effect of one-night Accepted for publication August 1990. Address correspondence and reprint requests to Prof. A. Baruzzi, Institute of Neurology, via Foscolo 7, 1-40123, Bologna, Italy.

CPAP treatment on plasma ANP and catecholamine concentrations in OSAS patients,

PATIENTS AND METHODS Six severe male OSAS patients (body mass index 36

± 6 kglm2; mean ± SD) aged 29-61 years (mean 41.3 ± 12.9 years) diagnosed on a preliminary polysomnographic night underwent conventional polysomnographic recordings including electroencephalogram (EEG), electrooculogram (EOG), electromyogram (EM G) of submental and intercostal muscles, microphone, electrocardiogram (ECG), oronasal thoracic, and abdominal respirogram by means ofthermistor and strain-gauge, ear oximetry (Biox III BTl, Boulder, CO) on two nights; the first in basal conditions (without treatment) and the second, two days later, with CPAP treatment (Sleep Easy I, Respironics, Monroeville, PA). Two patients had untreated mild hypertension whereas the others were within normal range. No patients had received CPAP treatment before this study and none were on drug therapy. 83

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A, Baruzzi, R, Riva, F. Cirignotta, M. Zucconi, M. Cappelli, and E. Lugaresi



TABLE 1. Sleep and respiratory measurements (mean ± SD) of the six patients studied with and without CPAP treatment Without CPAP

± 17 ± 25 ± 0.4 ± 20 ± II ± 8 a p < 0.03 Wilcoxon signed rank test.

Sleep duration (min) Stage 1-2NREM (min) Stage 3-4NREM (min) Stage REM (min) Event index Mean low Sa0 2 (%)

422 337 0.2 85 71 74

WithCPAP 385 162 98 125 4 89

± ± ± ± ± ±

39 38 a 38 a 49 2a la

Without CPAP Urine volume (mill 2 h) Sodium excretion (meq/12 h) Potassium excretion (meqll2 h) NA excretion (J.lglg creatinine) A excretion (!Lglg creatinine) HV A excretion (mglg creatinine) VMA excretion (mglg creatinine) ANP plasma cone! (pglml) NA plasma conc. b (pglml) A plasma conc. b (pglml)

902 150 44 95 6.7

± ± ± ± ±

297 33 24 101 9.1

2.8 ± 3.5 4.1 35 325 42

± ± ± ±

5.5 20 96 24

With CPAP 447 89 31 52 3.9

± ± ± ± ±

130a 35 a 15 16 a


2.1 ± 1.2 2.3 19 259 47

± ± ± ±

1.8 Sa 75 a


p < 0.035 Wilcoxon test. b Mean ± SD of the average value of each subject. NA = noradrenaline; A = adrenaline; ANP = atrial natriuretic peptide; HV A = homovanillic acid; VMA = vanillylmandelic acid. a

icantly. E.I. significantly decreased down to physiological values and, in the same way, the mean low Sa02 associated with each respiratory event significantly increased. Total sleep time was not significantly changed before or after CPAP, although on the second night, patients slept slightly less. There was a typical CPAP effect on slow-wave sleep that increased and on light NREM sleep that decreased. REM sleep did not significantly increase possibly because in two of the six patients there was a decrease on the second with respect to the first night. Nocturnal urine volumes, nocturnal natriuresis, and nocturnal noradrenaline excretion were significantly higher before than during CPAP treatment (Table 2). No effect of CPAP treatment was observed on nocturnal urinary excretion of adrenaline, homovanillic acid, vanilly1mandelic acid, or potassium (Table 2). Plasma ANP concentrations were higher during nontreated nights than during CPAP-treated nights (Table 2 and Fig. 1); moreover, ANP plasma concentrations showed wider fluctuations during nontreated nights than during CPAP treatment. Nocturnal plasma noradrenaline concentrations were significantly lower during CPAP treatment than before, whereas adrenaline concentrations during the two nights were similar (Table 2). Finally, there was a significant intersubject positive linear correlation during the nontreated night between ANP mean plasma concentrations and E.!. (r = 0.92 p < 0.01).

RESULTS As indicated in Table 1, CPAP treatment reversed apnea episodes almost completely in all our patients and consequently changed the quality of sleep signifSleep. Vol. 14. No. I. 1991

DISCUSSION The present study confirms the increased urinary water and sodium excretion during sleep in untreated

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Urine was collected during the two recording nights (from 8 p.m. to 8 a.m.) and a sample of each period was analyzed for Na+, K+, catecholamines, and their metabolites. Blood samples from a peripheral vein were collected in tubes containing EDT A each hour during the two recording nights from bedtime to the time of getting up in the morning by means of a venous catheter. Blood was immediately centrifuged at +4°C and plasma stored at - 80°C until analysis. Patients were not disturbed by blood drawing. No attempt was made to control fluid intake, and patients were kept on their usual diet. Plasma and urinary catecholamines were determined by high performance liquid chromatography with electrochemical detection (9), and plasma ANP was measured by radioimmunoassay (Amersham Inc., Amersham, UK) after chromatographic separation (1. 0). Sleep was scored in 30-s epochs according to the international criteria of Rechtschaffen and Kales (11). To simplify analysis of the data stages 1NREM and 2NREM were considered together [light nonrapid eye movement (NREM) sleep] as well as stages 3NREM and 4NREM (slow-wave sleep). Sleep desaturation was defined as the number of O 2 de saturation events (4% or greater drop in Sa0 2) per hour of sleep (event index, E.!.) (12). In severe stages of OS AS, desaturation eve:nts are always associated with obstructive apnea or hypopnea and total sleep time was almost all occupied by pathological respiratory events (13); therefore E.I. resembled the apnea + hypopnea index almost exactly. We also considered mean low SaOz (mean of the desaturation values of each E.!.) (12). CPAP was applied to the patients using a standard device and the pressure level was the minimum level that eliminated the obstructive event and snoring for each patient (means 11.2 ± 2.2 cm H 20). Statistical analyses were performed by means of the Wilcoxon test.

TABLE 2. Nocturnal urinary excretion of water, electrolytes, catecholamines and their metabolites, and nocturnal plasma concentrations of catecholamines and ANP (mean ± SD) in the six patients studied with and without CPAP treatment



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Atrial natriuretic peptide and catecholamines in obstructive sleep apnea syndrome.

Nocturnal polyuria with repeated micturitions during the night is a clinically evident feature of obstructive sleep apnea syndrome (OSAS). These effec...
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