pituitrin and Sleep-Apnea-Syndromes

Nasal obstruction is a risk factor in sleep-disordered breathing with a negative impact on the quality of life in humans. We investigated hydration changes produced by short term reversible, bilateral, nasal obstruction in young developing rat pups. Physiological parameters of growth (weight gain and gastric content weight) and dehydration were analyzed during two periods; during nasal obstruction at post-natal day 8 (days 9, 11 and 13), plus 7 and 90 days after recovery of nasal breathing (day 15 and adulthood). Body weight gain in oral breathing rat pups was slower compared to controls. Gastric weight was decreased significantly only in oral breathing rat pups on days 9 and 11 while plasma osmolality and vasopressin levels increased (indicators of dehydration). There were no differences between controls and treated rat pups by day 15, or at adulthood. Short term nasal obstruction-induced forced oral breathing, decreased gastric content which had a negative impact on growth and blood glucose concentration in the short term for female rat pups. Plasma corticosterone levels increased during the dehydration but were normal in males by 90 days. This could be a model for blocked nose syndrome in the newborn. Possible long term consequences on development are discussed.

Topics: Adrenal Cortex Hormones; Analysis of Variance; Animals; Animals, Newborn; Behavior, Animal; Blood Glucose; Body Weight; Dehydration; Female; Male; Mouth Breathing; Organ Size; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Wistar; Sleep Apnea Syndromes; Stress, Psychological; Time Factors; Vasopressins; Weight Gain

A co-morbidity of sleep-disordered breathing is hypertension associated with elevated sympathetic nerve activity, which may result from chronic intermittent hypoxia (CIH). CIH evokes plasticity in cardiorespiratory regulating sites, including the paraventricular nucleus (PVN), which acts to sustain increased sympathetic nerve activity. Our working hypothesis is that vasopressin neurons mediate the sustained increase in blood pressure and altered breathing associated with CIH. In a series of neuroanatomical experiments, we determined if vasopressin-containing PVN neurons innervate rostral ventrolateral medulla (RVLM), and altered cardiorespiratory responses induced by CIH conditioning (8h/day for 10 days) is mediated by vasopressin-V(1A ) receptor signaling in the medulla. In the first set of experiments, cholera toxin β subunit was microinjected into the RVLM to delineate innervation of the PVN. Immunohistochemistry data showed vasopressin-containing PVN neurons were double-labeled with cholera toxin β subunit, indicating vasopressin projection to the RVLM. In the second set, sections of the medulla were immunolabeled for vasopressin V(1A ) receptor, and its expression was significantly higher in the RVLM and in the neighboring rostral ventral respiratory column in CIH- than from RA-conditioned rats. In a series of physiological experiments,we determined if blocking the vasopressin V(1A )receptor in the medulla would normalize blood pressure in CIH-conditioned rats and also attenuate the evoked responses to PVN disinhibition.Blood pressure, heart rate, diaphragmatic and genioglossus muscle activity were recorded in anesthetized, ventilated and vagotomized rats. The PVN was disinhibited by microinjecting bicuculline before and after blocking vasopressin V(1A ) receptors in the RVLM/rostral ventral respiratory column. In RA-conditioned rats, PVN disinhibition increased blood pressure, heart rate, minute diaphragmatic and genioglossus muscle activity, and these increases were attenuated after blocking the vasopressin V(1A ) receptor. In CIH-conditioned rats, a significantly greater dose of blocker was required to blunt these physiological responses and it also normalized the baseline blood pressure. Our findings indicate that vasopressin is the neuropeptide released from PVN neurons that modulates cardiorespiratory output via the RVLM and rostral ventral respiratory column.

Topics: Animals; Bicuculline; Blood Pressure; Chronic Disease; Diaphragm; GABA-A Receptor Antagonists; Heart Rate; Hypertension; Hypoxia; Medulla Oblongata; Neurons; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Signal Transduction; Sleep Apnea Syndromes; Vasopressins

Topics: Aldosterone; Atrial Natriuretic Factor; Body Water; Guanosine Monophosphate; Hemodynamics; Humans; Positive-Pressure Respiration; Renin; Sleep Apnea Syndromes; Sodium; Vasopressins

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 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.) In patients with OSA, plasma ANP as well as urinary ANP excretion increased during the apneic period compared with the awake period. There was a significant negative correlation between plasma levels of ANP and ADH in patients with OSA. On the other hand, normal subjects had no apparent differences in plasma and urinary ANP levels between the two periods. It is suggested that nocturnal increase in ANP and decrease in ADH are responsible for the nocturnal diuresis and natriuresis associated with OSA.

Topics: Adult; Atrial Natriuretic Factor; Case-Control Studies; Circadian Rhythm; Diuresis; Female; Humans; Male; Middle Aged; Sleep; Sleep Apnea Syndromes; Vasopressins