Nitric oxide (NO) has been linked to many regulatory functions in mammalian cells. Studies of NO release are hampered by the short half-life of the molecule. In the blood, NO disappears within seconds because it binds avidly with haemoglobin (Hb). The relationship between Hb concentration and NO disappearance, however, has not been described. In this study we utilized an amperometric NO sensor (WPI, Sarasota, FL) to monitor continuously the disappearance of NO from an aqueous solution when Hb (free or as red blood cells) was added. The calibration and linearity of the NO sensor was checked frequently using a chemical reaction to generate a known concentration of NO. An aliquot of NO solution (prepared from authentic gas) was added to a glass beaker containing 20 ml saline to generate NO concentration of approximately 1200 nM. Under our experimental conditions (PO2 = 40 mmHg), NO concentration fell slowly over 20 min with a half-life of 445 s. However, when haemoglobin was added, NO disappeared rapidly in proportion to Hb concentration. The results suggest that rapid binding of NO to Hb occurs in a 4:1 ratio. The maximum rate constant of NO disappearance due to binding with Hb was 2 x 10(5) M-1 s-1. The 4:1 binding ratio between NO:Hb may be used as a tool to quantitate NO release in some biological assays. The study supports the notion that NO acts as an autocoid because it disappears rapidly in the presence of Hb and is not likely to act as a circulating humoral substance. The NO sensor was useful for monitoring of NO concentration in Hb free solutions, but its response time limits its use in blood.

We have investigated the effects of bolus administration of lignocaine 1.5 mg kg-1 i.v. on respiratory responses to airway irritation induced by instillation of distilled water into the trachea in 10 patients anaesthetized with enflurane (1.5% end-tidal). Before administration of lignocaine, airway irritation elicited not only the cough reflex, but also other respiratory reflexes such as expiration, apnoea and spasmodic panting. Immediately after administration of i.v. lignocaine, when plasma concentrations of lignocaine exceeded 4.7 micrograms ml-1, tracheal irritation elicited only brief apnoea. Other reflex responses were suppressed completely; they recovered gradually with progressive decrease in plasma concentration of lignocaine. The apnoeic reflex was not eliminated at plasma lignocaine concentrations greater than 7.0 micrograms ml-1, whereas the expiration reflex, cough reflex and spasmodic panting were eliminated effectively by plasma concentrations of lignocaine greater than 3.5, 2.8 and 2.2 micrograms ml-1, respectively.

The effects of constant positive airway pressure applied via a nose mask through the nares (nasal CPAP) on the swallowing reflex were studied in eight adult humans. The swallowing reflex was induced by bolus injections of a small amount of distilled water (0.5 ml) into the pharynx at four different values of endexpiratory airway pressure (0,5,10, and 15 cm H2O CPAP) or by continuous infusion of water (3 ml/min) at two different values of endexpiratory airway pressure (0 and 15 cm H2O CPAP). The latency of response from the time of bolus injection of water to the occurrence of the first swallow as well as the number of swallows elicited during the period of 10 s immediately following the water injection were measured. Our results showed that increases in endexpiratory airway pressure progressively prolonged the latency of response and decreased the number of swallows. Also, the frequency of swallows decreased greatly at nasal CPAP of 15 cm H2O during continuous infusion of water. These results indicate that nasal CPAP exerts an inhibitory influence on the swallowing reflex.

We have examined the sensitivity of the geniohyoid, an upper airway dilating muscle, to vecuronium in 12 anaesthetized dogs undergoing mechanical ventilation of the lungs and compared it with that of the diaphragm. Dogs were allocated randomly to two groups: pentobarbitone alone (group 1, n = 7); pentobarbitone combined with 0.2 MAC (0.44%) of enflurane anaesthesia (group 2, n = 5). Supramaximal single twitch stimulations (0.1 Hz) were applied to the phrenic nerves in the upper thorax and the geniohyoid branches of the hypoglossal nerves at the neck. The evoked responses were assessed by the transdiaphragmatic pressure (Pdi) and the isometric force of the geniohyoid muscles (Tgh) until complete recovery of these variables after i.v. administration of vecuronium 0.02 mg kg-1. In both groups, the magnitude of the depression of twitch response was greater and time required to reach control amplitude was longer in the geniohyoid than the diaphragm. The depression of Tgh was significantly greater in group 2 than in group 1, whereas no change was observed in Pdi between the two groups. We conclude that the geniohyoid is more sensitive to vecuronium than the diaphragm and the differential effects of vecuronium are facilitated by a low concentration of enflurane.

The effect of endogenous nitric oxide (NO) on the pulmonary hypoxic vasoconstriction was studied in isolated and blood perfused rat lungs. By applying the occlusion technique we partitioned the total pulmonary vascular resistance (PVR) into four segments: (1) large arteries (Ra), (2) small arteries (Ra'), (3) small veins (Rv'), and (4) large veins (Rv). The resistances were evaluated under baseline (BL) conditions and during; hypoxic vasoconstriction and acetylcholine (Ach) which was injected during hypoxic vasoconstriction. After recovery from hypoxia and Ach, Nomega-nitro-L-arginine (L-NA) was added to the reservoir and the responses to hypoxia and Ach were reevaluated. Before L-NA, hypoxia caused significant increase in the resistances of all segments (P < 0.05), with the largest being in Ra and Ra'. Ach-induced relaxation during hypoxia occurred in Ra, Ra' and Rv' (P < 0.05). L-NA did not change the basal tone of the pulmonary vasculature significantly. However, after L-NA, hypoxic vasoconstriction was markedly enhanced in Ra, Ra', and Rv' (P < 0.01) compared with the hypoxic response before L-NA. Ach-induced relaxation was abolished after L-NA. We conclude that, in rat lungs, inhibition of NO production during hypoxia enhances the response in the small arteries and veins as well as in the large arteries. The results suggest that hypoxic vasoconstriction in the large pulmonary arteries and small vessels is attenuated by NO release.