The interaction of angiotensin II and osmolality in the generation of sympathetic tone during changes in dietary salt intake. An hypothesis.

At rest, sympathetic nerves exhibit tonic activity which contributes to arterial pressure maintenance. Significant evidence suggests that the absolute level of sympathetic tone is altered in a number of physiologic and pathophysiologic states. However, the mechanisms by which such changes in sympathetic tone occur are incompletely understood. The purpose of this review is to present evidence that humoral factors are essential in these changes and to detail specifically an hypothesis for the mechanisms that underlie the changes in sympathetic tone that are produced during increases or decreases in dietary salt intake. It is proposed that the net effect of changes in dietary salt on sympathetic activity is determined by the balance between simultaneous and parallel sympathoinhibitory and sympathoexcitatory humoral mechanisms. A key element of the sympathoinhibitory mechanism is the chronic sympathoexcitatory effects of angiotensin II (ANG II). When salt intake increases, ANG II levels fall, and the sympathoexcitatory actions of ANG II are lost. Simultaneously, a sympathoexcitatory pathway is triggered, possibly via increases in osmolality which activate osmoreceptors or sodium receptors. In normal individuals, the sympathoinhibitory effects of increased salt predominate, sympathetic activity decreases, and arterial pressure remains normal despite salt and water retention. However, in subjects with salt-sensitive hypertension, it appears that the sympathoexcitatory effects of salt predominate, possibly due to an inability to adequately suppress the levels or actions of ANG II. The net result, therefore, is an inappropriate increase in sympathetic activity during increased dietary salt which may contribute to the hypertensive process.

Laryngeal-receptor responses to phasic CO2 in anesthetized cats.

We compared the effects of CO2 applied continuously and during expiration on laryngeal-receptor activity in paralyzed, artificially ventilated and nonparalyzed, spontaneously breathing cats by using an isolated larynx, artificially ventilated to approximate a normal respiratory cycle. The majority of quiescent negative-pressure and all cold receptors were excited by 5 and 9% CO2 applied both continuously and during expiration. In general, quiescent positive-pressure, tonic negative-pressure, and tonic positive-pressure receptors were inhibited by 5 and 9% CO2 applied continuously and during expiration. There were no significant differences between responses to 5 and 9% CO2 or to continuous and expired CO2 or between paralyzed and nonparalyzed preparations. In conclusion, laryngeal receptors respond to changes in CO2 concentration occurring during a normal respiratory cycle. Because laryngeal-receptor stimulation exerts reflex effects on ventilation and upper airway muscle activity, these results suggest that airway CO2 plays a role in reflex regulation of breathing and upper airway patency.

Assessment of fitness in patients with cystic fibrosis and mild lung disease.

BACKGROUND: Maximal exercise testing is used in patients with cystic fibrosis to assess functional status and prognosis. The lactate threshold is an index of aerobic fitness with significant advantages over maximal exercise tests. This study was undertaken to determine if the lactate threshold might be identified, non-invasively, in adult patients with cystic fibrosis and mild lung disease by measurement of ventilatory and gas exchange parameters. METHODS: Ten subjects with mild cystic fibrosis (forced vital capacity (FVC) > 70% predicted) and 10 healthy controls undertook an incremental exercise test on a bicycle ergometer. Ventilation and gas exchange parameters were measured continually and arterialised venous blood pH, carbon dioxide tension (PCO2), and lactate concentrations were measured at intervals throughout the tests. RESULTS: In subjects with cystic fibrosis there was no significant difference between the mean gas exchange and lactate thresholds (mean difference 1.0 (95% confidence interval (CI) of the mean -1.5 to 3.44) ml/kg/min). In contrast, there was a significant difference between the mean ventilatory and lactate thresholds (3.8 (95% CI 0.9 to 6.7) ml/kg/min). Arterialised venous PCO2 increased significantly during the exercise tests. In healthy subjects the mean differences between these thresholds were not significantly different from zero and PCO2 fell significantly during the tests. CONCLUSIONS: The ventilatory threshold significantly overestimates the lactate threshold in subjects with cystic fibrosis induced lung disease because of impaired carbon dioxide excretion during exercise. However, the gas exchange threshold may be used to determine the lactate threshold in this patient group.

The effects of oesophageal distension on diaphragm and laryngeal muscle activity in the anaesthetized cat.

The electromyographic (EMG) activities of diaphragm and laryngeal muscles were recorded during oesophageal distension in anesthetized cats. The responses to distension of the thoracic oesophagus differed from those evoked by distension of the cervical oesophagus. The crural component of the diaphragm (CD) was inhibited by distension of the thoracic oesophagus; distension of the cervical oesophagus did not affect CD EMG. Thyroarytenoid (TA) muscle EMG increased markedly and consistently in response to distension of the cervical oesophagus. Distension of the thoracic oesophagus only produced statistically significant increases in TA EMG with high distending volume (10 ml) at the level of the gastro-oesophageal junction. The main abductor of the vocal cords, the posterior cricoarytenoid (PCA) was either unchanged or decreased by oesophageal distension. The electrical activities of left paratendinous diaphragm, left costal diaphragm, internal intercostal and external intercostal muscles remained unchanged. The entire pattern would appear to constitute a means to aid passage of a bolus into the stomach, and simultaneously guard the respiratory tract from reflux or aspiration.

Carbon dioxide-sensitive superior laryngeal nerve afferents in the anaesthetized cat.

The effects of CO2 on laryngeal receptors were studied in ten anaesthetized, paralysed, artificially ventilated cats using a preparation in which the upper airway was isolated in situ and artificially ventilated. This allowed CO2 to be confined to the upper airway and enabled responses to CO2 to be recorded whilst the larynx was being ventilated under physiological conditions. Single-unit afferent activity was recorded from the superior laryngeal nerve and the pressure and thermal sensitivity of receptors determined. Carbon dioxide responses were tested by switching from upper airway ventilation with room air to mixtures containing 5 and 9% CO2 with 21% O2 in N2. Fibres were classified into two broad groups, tonic and quiescent, depending on their level of activity when the larynx was not being ventilated. All tonic fibres responded to either positive or negative pressure. Quiescent fibres were either positive or negative pressure receptors, cold receptors or had no response to pressure or cold airflow. The majority of all categories of fibres were significantly affected by CO2 in a reversible and usually concentration-dependent manner. Tonic fibres were inhibited, regardless of pressure sensitivity. Quiescent negative and positive pressure receptors were excited and inhibited respectively whilst cold receptors and fibres with no response to occlusion were excited. Laryngeal hypoxia and systemic asphyxia and hypercapnia had no effect on receptor activity. We conclude that the majority of laryngeal receptors are sensitive to CO2 and that this receptivity may be important in the control of ventilation and upper airway muscle activity.

The responses of superior laryngeal nerve afferent fibres to laryngeal airway CO2 concentration in the anaesthetized cat.

In anaesthetized cats, the isolated, in situ, larynx was subjected to a simulated respiratory cycle and the responses of fifty-six superior laryngeal nerve (SLN) afferent fibres to respiration-related stimuli were examined during changes in the fractional CO2 concentration of the laryngeal airway (Faw, CO2). Sensory SLN fibres which displayed low rates of discharge when the larynx was unventilated (quiescent fibres) and which responded to negative laryngeal airway pressure were excited by elevations in Faw, CO2 whereas quiescent fibres responsive to positive laryngeal pressure were inhibited by the same procedure. We propose that changes in airway CO2 levels may play a role in maintaining upper airway patency, especially during sleep.

The effects of changes in laryngeal airway CO2 concentration on genioglossus muscle activity in the anaesthetized cat.

In the anaesthetized cat the larynx was isolated in situ, artificially ventilated and used to assess reflex effects exerted by respiration-related laryngeal stimuli on genioglossus electromyographic activity (Gg EMG) and respiratory frequency (RF). Phasic Gg EMG was not observed when the larynx was unventilated but was evoked, with a concurrent decrease in RF, when negative pressures or oscillatory pressures similar to those of normal ventilation were applied to the larynx. Increases in laryngeal airway CO2 concentration also enhanced Gg EMG and reduced RF. All reflex effects were abolished by bilateral section of the superior laryngeal nerves. We propose that negative intralaryngeal pressure and CO2 may act together to restore pharyngeal patency during obstructive apnoea.