Original Paper Respiration 1992;59:164-168

Masahiko Ichioka Yukio Hirata Naohiko Inase Naoko Tojo Masafwni Yoshizawa Mamoru Chula Itsuro Miyazato Satoshi Taniai Fumiaki Mantmo

Changes of Circulating Atrial Natriuretic Peptide and Antidiuretic Hormone in Obstructive Sleep Apnea Syndrome

Second Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Abstract Patients with obstructive sleep apnea (OSA) syndrome are known to exhibit nocturnal natriuresis/diuresis. We studied plasma and urinary levels of atrial natriuretic peptide (ANP), a potent natriuretic hormone released from the heart, and plasma antidiuretic hormone (ADH) levels in patients with OSA during awake and sleeping periods, to compare with those of normal subjects. Seven patients with OSA and 6 normal subjects were studied. Arterial blood samples were drawn during the awake and the sleeping period, while in pa­ tients with OSA, blood samples were obtained during the apneic period. Urine samples were collected over two 12-hour periods (9 a.m-9 p.m. and 9 p.m.-9 a.m.) In patients with OSA, plasma ANP as well as urinary ANP excretion in­ creased during the apneic period compared with the awake period. There was a significant negative correlation between plasma levels of ANP and ADH in pa­ tients with OSA. On the other hand, normal subjects had no apparent differ­ ences in plasma and urinary ANP levels between the two periods. It is sug­ gested that nocturnal increase in ANP and decrease in ADH are responsible for the nocturnal diuresis and natriuresis associated with OSA.

Introduction In patients with obstructive sleep apnea (OSA) syn­ drome. nocturnal enuresis is a common symptom [1], A re­ cent study showed that patients with OSA had greater nocturnal diuresis and natriuresis than normal subjects [2], However, the mechanism of the increased urinary out­ put and the excretion of sodium during the night in OSA has not been clear. Atrial natriuretic peptide (ANP), isolated and purified

Received: May 16. 1991 Accepted after revision: February 27,1992

from human cardiac atria [3], has been shown to be a novel circulating hormone with a potent natriuretic, diuretic and vasodilatory effect that regulates the extracellular fluid volume and blood pressure. To evaluate whether endogenous ANP contributes to the nocturnal diuresis and natriuresis in OSA, we mea­ sured plasma and urinary ANP levels as well as various cir­ culating hormones during awake and sleeping periods in patients with OSA and in normal subjects.

Masahiko Ichioka. Ml) Second Department of Internal Medicine Tokyo Medical and Dental University 5*45. Yushimu 1-chôme. Bunkyo-ku Tokyo 113 (Japan)

© 1992S.KargerAG,Basel 0025-7931/92/0593-0164 $ 2.75/0

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Key Words Obstructive sleep apnea syndrome Atrial natriuretic peptide Nocturnal natriuretic diuresis Antidiuretic hormone

Subjects Seven patients with OSA and 6 normal subjects were studied. In­ formed consent was obtained from each individual. The patients with OSA comprised 6 men and I woman, aged 21-58, who fulfilled the polysomnographic criteria of OSA by Guilleminault et al. [11. The apnea index was established as the ratio of the number of the apneic epi­ sodes to the sleep duration. Sleep apnea was diagnosed in patients who had an apnea index of greater than 5/h. OSA was diagnosed in patients who exhibited chest wall and abdominal expansion during the apncic periods. No patients with OSA had cardiovascular disease, hypertension, or renal disease except for I patient. This patient was treated with furosemide and digitalis due to idiopathic cardiomyo­ pathy but he was free from heart failure during this study. The normal subjects comprised 6 men, aged 25-55, who were in good health and not taking any medications. Methods In the polysomnographic study, electroencephalogram, electroocculogram, clcctromyogram, electrocardiogram, chest wall and abdominal movement, and oronasal air flow were recorded. In addi­ tion to the standard polysomnographic recording, oxyhemoglobin saturation (SaO,) by transcutaneous oxymetry (502 Pulse Oximeter, CSI Japan) was recorded from 9 p.m. until 6 a.m. Prior to the sleeping period, all subjects had a brachial artery catheter inserted percutaneously. Two blood samples were drawn from normal subjects and OSA patients in supine position, one during the awake period (10 a.m.) and another during the sleeping period (10 p.m.-6 a.m.), while in patients with OSA, blood samples were obtained during the apneic period. Urine samples were collected over two 12-hour periods (9 a.m.-9 p.m. and 9 p.m.-9 a.m.). Plasma and urine ANP levels were determined by highly sensitive radioimmunoassay as previously described [4], Plasma antidiuretic hormone (ADH), plasma renin activity, aldosterone, and cortisol were measured by their specific radioimmunoassays. Plasma epine­ phrine and norepinephrine were measured by high-performance liq­ uid chromatography. Serum sodium, potassium, and chloride were measured by ion-selective electrodes. Scrum and urinary creatinine was measured by flame method, and urinary chloride was measured by tripyridyl triazine assay. Subject Characteristics Clinical and polysomnographic characteristics of the patients with OSA (n = 7) and normal subjects (n = 6) are listed in tabic I. Ex­ cept that the patients with OSA weighed more (p

Changes of circulating atrial natriuretic peptide and antidiuretic hormone in obstructive sleep apnea syndrome.

Patients with obstructive sleep apnea (OSA) syndrome are known to exhibit nocturnal natriuresis/diuresis. We studied plasma and urinary levels of atri...
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