Either excitatory or inhibitory cardio-respiratory responses induced by nicotine have been reported. We evaluated the joint and separate contributions of peripheral arterial chemoreceptors and pulmonary vagal afferences to nicotine-induced cardio-respiratory responses in 11 pentobarbitone-anaesthetized cats. Nicotine, given i.v. in doses of from 1 to 200 microg/kg, evoked dose-dependent transient increases in tidal volume (VT) and arterial blood pressure (BP), but the highest doses evoked brief apnoea, immediately followed by intense hyperventilation, as well as discrete early hypotension followed by late hypertension. Bilateral section of the aortic and carotid nerves abolished all hyperventilatory responses to nicotine, giving way to apnoea followed by few cycles of reduced VT and profound hypotension followed by slight hypertension in response to intermediate doses (50-100 microg/kg). Subsequent bilateral vagotomy (BV) suppressed apnoeic and hypotensive responses. In other cats initially subjected to BV, only increases in VT and BP were observed in response to nicotine, effects which were no longer observed after additional carotid and aortic deafferentation. These data suggest that excitatory effects of nicotine on respiration and BP are reflexes evoked by stimulation of peripheral arterial chemoreceptors, while inhibitory effects are also reflex responses but evoked from stimulation of pulmonary vagal afferences.

The carotid bodies are composite receptors, i.e. hypoxia apparently acts upon glomus cells which are synaptically apposed to the sensory endings of primary afferent neurons, responsible for conveying the information to the medullary centers. Considerable effort has been directed to determine the transmitter(s) involved in signal transference between glomus cells and chemosensory nerve terminals. Dopamine is the putative transmitter that has received more attention, because of the following observations: i) glomus cells are characterized by their abundance in dense-core granules and strong formaldehyde-induced fluorescence, indicative of a high concentration of catecholamines (see Hess, 1975); ii) dopamine is the prevalent catecholamine in the carotid body of most species studied (see Fidone et al, 1983); iii) glomus cells possess the enzymes required for dopamine synthesis as well the transporter mechanisms for uptake of dopamine and its precursors (see Eyzaguirre & Zapata, 1984); iv) the dopamine content of the rat carotid body in situ is reduced in direct proportion to the severity and duration of hypoxia (Hellström et al, 1976; Hanbauer & Hellström, 1978); v) the dopamine content of the rabbit carotid body in vitro is reduced by hypoxic superfusates (Leitner, 1993); and vi) hypoxia induces dopamine release from rabbit and cat carotid bodies superfused in vitro (Fidone et al, 1982; Rigual et al, 1986; see also Zapata et al, 1996). These observations led to the proposal that dopamine may serve as the excitatory transmitter between glomus cells and chemosensory nerve terminals (see Gonzalez et al, 1994).

While the chemoreceptor discharges of carotid bodies in vitro are highly dependent on temperature, these chemoreceptors in situ contribute only moderately to the ventilatory adjustment to changing body temperature (Tb), probably because of the concomitant and reverse changes in natural chemoreceptor stimuli in closed-loop preparations. Accordingly, we studied the frequency of carotid chemosensory discharge (fx) and the phrenic integrated electroneurogram (IENGph) in pentobarbitone anesthetized cats, paralyzed with alcuronium and artificially ventilated, at three steady-state levels of Tb (35.5, 37.5 and 40.2 degrees C), modifying the frequency and volume of the ventilator to maintain PETCO2 within normal range. While fx increases along with Tb when PETCO2 is allowed to fluctuate freely, its mean basal value was not consistently different at the three Tb's studied under controlled conditions. The amplitude of IENGph was reduced and the frequency of phrenic inspiratory cycles was increased as Tb was raised from 35.5 to 37.5 degrees C and then to 40.2 degrees C. Brief 100% O2 inhalations and i.v. injections of dopamine produced minimal depressions of IENGph amplitude in hypothermia, but pronounced although similar depressions in normothermia and hyperthermia. i.v. injections of NaCN augmented fx and IENGph in dose related manner, and the relationships between both variables showed larger changes in IENGph at the hypothermic and normothermic conditions when expressed in absolute terms, but not when expressed in relative terms. Thus, the chemosensory input is not consistently modified by thermal levels under controlled ventilatory conditions, but the chemosensory drive of the ventilatory output is less pronounced in hypothermia. The chemosensory input is similarly affected by varying degrees of cytotoxic hypoxia at different Tb's, but the ventilatory output is less vigorously increased in hyperthermia, pointing to a decreased reflex gain in that condition.

The effects of domperidone, antagonist of D2 receptors, on arterial chemoreceptor activity were studied in spontaneously breathing and pentobarbitone anesthetized cats, in which recordings of chemosensory impulse activity were obtained simultaneously from both cut carotid (sinus) nerves. Intravenous injections of domperidone 50 μg/kg produced a maintained increase in the basal frequency of chemosensory discharges, after which hyperoxic tests (breathing 100% O2 for 30 s) evoked larger falls in the rate of chemosensory impulses. Chemosensory responses evoked by hypoxic hypoxia (100% N2 tests) and by cytotoxic hypoxia (i.v. injections of NaCN) reached higher impulse rates after domperidone treatment. The effects of domperidone reveal that a resting release of dopamine from glomus cells maintains a low level of basal chemosensory activity under normoxic conditions. Domperidone turns off such restraining dopaminergic control and enhances the transient chemosensory responses to hypoxic stimuli. Present data support a modulatory role for dopamine within the chemoreceptor process, but not its participation as excitatory transmitter between glomus cells and sensory nerve endings.

It has been shown that the frequency of chemosensory discharges recorded from carotid bodies superfused in vitro is highly dependent on temperature (Gallego et al., 1979), presenting both dynamic and static components (Eyzaguirre and Zapata, 1984). Such thermal influence had also been observed in carotid bodies in situ, in which the rate of chemosensory discharges increased in response to local warming of the arterial blood circulating through the carotid bifurcation (McQueen and Eyzaguirre, 1974). The high energies of apparent activation (μ.) and high thermal coefficients (Q10) exhibited by the rate of discharges of these preparations indicate that the carotid body chemoreceptors fulfil the criteria for being considered as potential thermosensors.

1. We studied the total amount and subcellular distribution of alveolar surfactant, extracted through bronchoalveolar lavage of anesthetized cats and rabbits. This was correlated to several morphometric and ventilatory variables of these animals. 2. Lung weight was significantly larger in the cat while respiratory frequency and minute ventilation were significantly larger in the rabbit. No significant differences were observed in tidal volume, total lung capacity, P(a)O2, P(a)CO2 and pH(a). 3. While both species had similar protein contents in the bronchoalveolar lavage, rabbits had larger phospholipid contents, mostly distributed in the lighter, more active subfractions. 4. With regard to the estimated values obtained from allometric equations derived for mammals, the rabbit presented a lung weight of nearly one-third of the estimated one, an exceedingly larger minute ventilation (by nearly 60%) and a respiratory frequency twice the calculated one. 5. We suggest that the different distribution of alveolar surfactant in these species may be explained by disparities in their ventilatory demands, the rabbit having a higher respiratory frequency and a larger minute ventilation, performed by a mass of lung tissue lower than that corresponding to its body mass.

The effects of changes in body core temperature (TB) upon the frequency of chemosensory discharges (fx) from one carotid nerve were studied in pentobarbitone anesthetized cats. Raising TB from 35 to 40 degrees C increased fx in some cats, an effect more commonly seen after contralateral carotid neurotomy. In other animals, the simultaneously increased alveolar ventilation counteracted the above effect. A multiple correlation analysis of global data showed predicted increases in fx in response to raising TB at different CO2 levels.

In pentobarbitone anesthetized cats, raising body temperature from 37 to 40-degrees-C by external heat increased respiratory frequency, tidal volume, frequency of spontaneous gasps and mean inspiratory flow. It reduced end-tidal CO2 pressure, together with inspiratory and expiratory durations. After bilateral section of the carotid nerves, raising body temperature still induced hyperventilation, but the increase in gasp frequency was less pronounced and no significant change in tidal volume was observed. In comparison to steady ventilatory values in the intact condition, significant reductions in tidal volume at 38-degrees-C and in gasp frequency at 37, 39 and 40-degrees-C were observed after bilateral carotid neurotomy. Brief hyperoxic tests induced transient decreases in tidal volume and increases in end-tidal CO2 pressure which were significantly larger at 40-degrees-C than at 37-degrees-C. These changes disappeared after bilateral carotid neurotomy. Anesthetic block of both carotid nerves produced transient reductions in tidal volume at any given temperature. We conclude that carotid body afferents contribute to the hyperventilation evoked by hyperthermia. After their interruption, such contribution is replaceable from other thermal afferents.

Few studies have been done to establish the ventilatory factors affecting alveolar surfactant under resting conditions. Experiments in which ventilatory variables were recorded for 4 h were performed in 12 adult cats breathing spontaneously under pentobarbital sodium anesthesia. After the animals were killed and bronchoalveolar lavages (BALs) were performed, the resulting fluid was subjected to differential centrifugation and determinations of proteins, phospholipids (PL), and disaturated phosphatidylcholine (DSPC). Pellet P1+2 was obtained by two centrifugations at 140 g; the supernatant was centrifuged at 1,000 g to obtain pellet P3 and subsequently at 60,000 g to obtain P4. Pellets P3 and P4 had the higher contents of PL and DSPC. Bivariate and multivariate correlational analyses indicate that 1) total PL in BAL was not related to any of the ventilatory variables studied, 2) PL in P3 and P4 fractions was directly correlated to the physiological range of variations in the frequency of large spontaneous gasps (fL), and 3) PL in P1+2 fraction was inversely related to fL. Cats subjected to bilateral section of carotid nerves, although presenting reduced chemosensory drive and ventilatory chemoreflexes, did not exhibit significant differences in resting ventilatory variables nor in alveolar surfactant components. Present results indicate that the total content of alveolar surfactant is not modified by ventilatory variations within physiological range but that the spontaneous occurrence of large gasps increases the proportion of more active forms of alveolar surfactant. This may mediate the role of augmented breaths in keeping lung compliance and preventing atelectasis under resting ventilatory conditions.