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We studied the effect of chronic hypobaric hypoxia (CHx; 10-11% O(2)) on the response to hypercapnia (15% CO(2)) of individual solitary complex (SC) neurons from adult rats. We simultaneously measured the intracellular pH and firing rate responses to hypercapnia of SC neurons in superfused medullary slices from control and CHx-adapted adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. We found that CHx caused the percentage of SC neurons inhibited by hypercapnia to significantly increase from about 10% up to about 30%, but did not significantly alter the percentage of SC neurons activated by hypercapnia (50% in control vs. 35% in CHx). Further, the magnitudes of the responses of SC neurons from control rats (chemosensitivity index for activated neurons of 166+/-11% and for inhibited neurons of 45+/-15%) were the same in SC neurons from CHx-adapted rats. This plasticity induced in chemosensitive SC neurons by CHx appears to involve intrinsic changes in neuronal properties since they were the same in synaptic blockade medium.

Isocapnic hypoxic ventilatory response (HVR) and hematological variables were measured in nine adult males (age: 29.3+/-3.4) exposed to normobaric intermittent hypoxia (IH, 2 h daily at FI(O(2))=0.13, equivalent to 3800 m altitude) for 12 days. Mean HVR significantly increased during IH, however, after reaching a peak on Day 5 (0.79+/-0.12 vs. 0.27+/-0.11 L.min(-1).%(-1) on Day 1, P<0.05), it progressively decreased toward a lower value (0.46+/-0.16 L min(-1) x %(-1) on Day 12). In contrast, the subjects showed no changes in the ventilatory data and arterial O(2)-saturation in normoxia or poikilocapnic hypoxia (PET(CO(2)) uncontrolled). Hematocrit and hemoglobin concentration did not change, but the reticulocyte count increased by Day 5 (P<0.01). Our results suggest that moderate intermittent hypoxia induces changes in ventilatory O(2)-sensitivity and triggers the hematological acclimatization by increasing the percentage of reticulocytes in the blood. Normal ventilatory acclimatization to hypoxia was, however, not observed and the mechanisms involved in the biphasic changes in HVR we observed remain to be determined.

The responses of avian arterial chemoreceptor preparations to 44-sec steps of inspired CO2 and O2 were quantified. Anesthetized ducks were unidirectionally ventilated, arterial pH was recorded with a fast responding indwelling electrode, and neural activity was recorded from 28 preparations consisting of dissected filaments of the vagus nerve (23 single-fibered, 5 few-fibered). We analyzed responses using cycle-triggered stimulus histograms of neural discharge, cross correlation analysis, and analysis of variance. Average responses of the chemoreceptor preparations to PaCO2 steps from 24 +/- 1 to 38 +/- 1 Torr were larger (per Torr), occurred faster, and appeared more rate sensitive than the responses to PaO2 steps from 101 +/- 3 to 56 +/- 2 Torr. Average responses to CO2 steps usually appeared more rate sensitive when measured during arterial hypoxia than during arterial normoxia. These characteristics are very much like those reported for mammalian arterial chemoreceptors, except that responses of avian chemoreceptor preparations to repetitive CO2 steps were highly variable according to statistical analysis.

We studied the effects of hypercapnia (FICO2 = 0.07) and hypoxia (FIO2 = 0.13) on the cricothyroid muscle response (peak integrated CT EMG) to graded inspiratory resistance (RI). Five anesthetized dogs spontaneously breathed through the upper airway (UAB) or a side arm of a tracheotomy cannula bypassing the larynx (TB). With room air UAB, graded increases in RI increased CT EMG, upper airway pressure change (Paw) and esophageal pressure change (Pes, indicating increased inspiratory drive), but decreased VT. For room air TB, the effects of RI were much less but still significant. Hypercapnia increased VT, fR, Pes, Paw and CT EMG for any given RI during UAB more than during TB. Hypoxia increased fR but did not increase VT, Pes, Paw, or CT EMG. The results are consistent with a model predicting CT activity as additive functions of inspiratory drive and laryngeal receptor stimulation by Paw and no direct effects of chemoreceptor stimulation on the CT, independent of those resulting from changes in inspiratory drive and upper airway pressure.

We tested the hypothesis that altitude-induced hypocapnia in hens reduces eggshell conductance to water vapor (GH2O). Seven laying hens (Gallus domesticus) native to 1200 m were chronically exposed to high altitude (3800 m), and then to high altitude with sufficient inspired CO2 to relieve hypocapnia (3800 m + CO2). Egg GH2O was measured gravimetrically, shell thickness was measured with a micrometer, and aggregate pore area was calculated from measured values using Fick's law. Comparing results at 1200 m (n = 118) and 3800 m (n = 102), GH2O was reduced from 13.9 +/- 0.2 to 12.6 +/- 0.2 mg/(d.Torr)(mean +/- SE), shell thickness was reduced from 0.297 +/- 0.003 mm to 0.287 +/- 0.003 mm, and calculated aggregate pore area per egg was reduced from 1.97 +/- 0.03 mm2 to 1.72 +/- 0.03 mm2. When hypocapnia was relieved at 3800 m + CO2 (n = 82), GH2O was reduced even further to 11.1 +/- 0.2 mg/(d.Torr), shell thickness increased to 0.305 +/- 0.003 mm, and aggregate pore area was reduced to 1.61 +/- 0.03 mm2. Based on these results we reject our hypothesis. We conclude that hypocapnia is responsible for thin eggshells at altitude. Other physiological stimuli must cause the reductions in eggshell GH2O and pore area.

The effects of body temperature (Tb) on pulmonary stretch receptor (PSR) and CO2-sensitive intrapulmonary chemoreceptor (IPC) response characteristics may have important effects on ventilatory control in reptiles. In this study, three questions were addressed: (1) what are the effects of Tb on PSR and IPC responses to airway pressure (Paw) and lung CO2 (PCO2); (2) what are the effects of acute (less than 12 h) vs chronic (greater than 1 week) changes in Tb on both receptor groups; and (3) can predicted changes in the fractional dissociation of imidazole (alpha im), calculated via independent changes in Tb and PCO2, explain the CO2-sensitivity of either IPC or PSR? Single fiber PSR and IPC responses to Paw, PCO2 and Tb were determined in 11 anesthetized Alligator mississippiensis (pentobarbital; 30 mg/kg), acclimated at 20 degrees C (N = 5) or at 30 degrees C (N = 6). PSR activity increased as Paw increased at both Tb, but PSR activity and sensitivity to Paw were lower at 20 degrees C. The average Q10 was 2.1. Increasing inhaled CO2 from 1 to 7% decreased PSR activity by 27 +/- 6% at 20 degrees C and 18 +/- 5% at 30 degrees C. IPC activity decreased as PCO2 increased at both Tb, but IPC activity and sensitivity were reduced at 20 degrees C. The average Q10 was 3.2. Increasing Paw from 2 to 10 cm H2O had inconsistent effects on IPC activity. There were no differences between the effects of acute or chronic changes in Tb on either PSR or IPC responses. Predicted changes in alpha im could not explain the CO2-sensitivity of either IPC or PSR. We conclude that PSR and IPC adapt rapidly to Tb changes. The larger Q10 of IPC suggests that the relative role of IPC vs PSR in ventilatory control may be greater at elevated body temperatures.

Ventilation and blood gases were measured in unanesthetized ducks at various levels of inspired CO2 partial pressure (PICO2). Ventilation was markedly augmented with increasing PICO2, whereas arterial and mixed venous PCO2 stayed essentially constant up to a PICO2 of about 20 torr and changed only slightly between that and the highest level tested (34 torr). After carbonic anhydrase had been blocked, blood PCO2 was elevated at all levels of PICO2 but the ventilatory response to increases in PICO2 were attenuated. The response to CO2 in the normal bird (before administration of acetazolamide) shows similarities to that in mammals. Qualitative differences between both classes of vertebrates after blockade of carbonic anhydrase may, however, suggest differences in their systems that control ventilation.

The effects of airway CO2 and pressure on pulmonary vagal afferent fibers were studied in seven anesthetized alligators Alligator mississippiensis, at room temperature (24 degrees C). Of 49 receptors which fired in phase with ventilation, 13 behaved like mammalian rapidly adapting pulmonary stretch receptors, 19 like mammalian slowly adapting pulmonary stretch receptors (PSR), and 17 like avian intrapulmonary CO2-sensitive chemoreceptors (IPC). PSR and IPC were positively localized to the lung by punctate stimulation or response to airway CO2 changes during pulmonary artery occlusion. PSR discharge frequency (fPSR) was measured at airway pressures (Paw) from 0 to 15 cm H2O at FICO2 = 0.01 in 14 receptors. fPSR increased in all receptors throughout the range of Paw studied. In 13 PSR, increasing FICO2 from 0.01 to 0.07 decreased fPSR 23 +/- 13% (+/- SEM) at Paw = 2 cm H2O and 14 +/- 7% at 15 cm H2O. IPC discharge frequency (fIPC) decreased as FICO2 increased and most discharged less than 1 sec-1 at FICO2 = 0.03. In 7 IPC at FICO2 = 0.01, increasing Paw from 2 to 15 cm H2O increased fIPC 17 +/- 5% after pulmonary artery occlusion demonstrating some mechanosensitivity in alligator IPC. Although both IPC and PSR showed mechanosensitivity and CO2-sensitivity, the two receptor types were distinct. PSR were 13 times more sensitive to Paw changes than IPC and IPC were 14 times more sensitive to FICO2 changes than PSR. We did not find any receptors with intermediate CO2- or mechanosensitivities that could represent a transitional form of receptor. These results predict that IPC and PSR may have different roles in reflex ventilatory control.

We investigated the influence of intrapulmonary chemoreceptors (IPC) on ventilatory movements in anesthetized chickens when PCO2 profiles along the parabronchi were changed. In all experiments the right lung was denervated, both lungs unidirectionally ventilated, and PaCO2 kept constant. In series 1 (7 birds), gas flow and the PCO2 profile in the left lung were reversed. PaCO2, PECO2 and ventilatory movements did not change. In Series 2 (4 birds), PCO2 in caudal regions of the innervated lung was elevated by increasing gas flow and P1CO2 from 0 to 21 Torr. Ventilatory movements did not change. In Series 3 (4 birds), either lung was over-ventilated with 7 or 49 Torr P1CO2, alternating the gases between lungs every 100 sec. Ventilatory movements changes with P1CO2 but much less than predicted from P1CO2 effects in the non-perfused, innervated lung. From the longitudinal distribution of IPC and PCO2 profiles in the lung we predicted moderate to large changes in ventilatory movements in all series. The discrepancy between predicted and observed results in Series 1 and 2 indicates that IPC in caudal regions of the lung have little effect on ventilation under the conditions examined. In Series 3, observed ventilatory movements were less sensitive to P1CO2 than predicted, indicating that IPC sense a different PCO2 than the PCO2 profile in the parabronchial lumen and that IPC have a significant sensitivity to pulmonary blood PCO2.

The role of intrapulmonary chemoreceptors in the breath-to-breath control of spontaneous breathing was studied in anesthetized ducks by stimulating these receptors with changes in mixed venous CO2 loads during prolonged circulation time to the carotid bodies and brain by vascular loops placed in both brachiocephalic arteries. Blood equilibrated with gas mixtures of high (85% CO2-15% O2) or low CO2 (air) was infused into the right ventricle at 100 ml . min-1, while simultaneously withdrawing blood from the entrance of the right atrium at the same rate. A variety of cardiopulmonary and blood gas variables were measured. Infusing blood of high PCO2 increased both respiratory frequency and tidal volume long before the altered blood could have reached the carotid bodies or brain. The increase in ventilation was not enough to prevent a rise in PaCO2. Infusing blood of low PCO2 decreased both respiratory frequency and tidal volume. Again, the changes in respiration occurred before the infused blood had reached the carotid bodies or the brain. Infusion of blood similar in PCO2 to mixed venous blood did not significantly alter ventilation or arterial blood gases. The rapidity of the ventilation response to a change in mixed venous CO2 load led us to conclude that the intrapulmonary chemoreceptors can detect changes in mixed venous CO2 loads and that they initiate a ventilatory change appropriate to minimize alterations in PaCO2. These receptors, thus, can control breathing on a breath-to-breath basis in birds.

We have estimated the relative importance of changes in blood PCO2 and pH in determining activity of intrapulmonary chemoreceptors (IPC) in the unidirectionally ventilated duck. The response of single unit vagal afferents from IPC to changing lung gas PCO2 was tested before and after changing blood pH by intravenous infusion of NaHCO3. Using multiple linear regression analysis, we calculated how much of the change in IPC activity for a given change in PCO2 was due to the changing PCO2 at constant pH (CO2 sensitivity) or to the change in pH concomitant with the change in PCO2 (H+ sensitivity). For 10 IPC, the CO2 sensitivity was on the average 2.3 times larger than the H+ sensitivity. Changes in pH as well as PCO2 of lung blood should be considered in assessing the role of IPC in control of breathing.

The CO2 sensitivity of intrapulmonary CO2 receptors (IPC) in the duck was studied, before (Control) and after blockade of carbonic anhydrase by Diamox, by recording single unit afferent activity in the vagus nerve. During Control, IPC activity decreased with increasing airway CO2 concentration. After Diamox administration, the discharge from IPC was higher at all levels of airway PCO2, and the receptors' CO2 sensitivity was markedly attenuated. Comparing these results with measurements on ventilation and blood gases of the duck under similar experimental conditions (Powell et al., 1978b) suggests that IPC play a role in the adjustment of ventilation to altered concentrations of inspired CO2; IPC may thus be a significant component in the control of breathing under physiological conditions.

The steady-state discharge of fourteen arterial chemoreceptor preparations were recorded from the left cervical vagi of unidirectionally ventilated, pentobarbitone anaesthetized ducks. All were excited by both hypoxia and hypercapnia and these stimuli interacted multiplicatively, as they do in mammals. We located the receptive fields of three preparations by observing their responses to i.v. injections of 2,4-dinitrophenol before, during and after occlusion of various arteries. The responses of two preparations were consistent with their location in the ipsilateral carotid body, but the responses of one, containing two active fibres, suggested that its discharge originated in aortic bodies. The discharge of eleven preparations was not random, but came in short high frequency bursts. As stimulus intensity was increased by either hypoxia or hypercapnia the average number of impulses per burst decreased. We have shown that the arterial chemoreceptors of the duck are sensitive to both hypoxia and hypercapnia. Because the steady-state stimulus-response characteristics are essentially the same as those of mammals we suppose that both mammalian and avian chemoreceptors are excited by the same basic mechanism. We also show that ducks have active extra-carotid arterial chemoreceptors.

CO2 tensions in the caudal air sacs of birds cannot be quantitatively predicted by current models of avian respiration, mainly because the contribution of neopulmonic parabronchial gas exchange has not been determined. To overcome this problem we studied penguins that have purely paleopulmonic lungs. Three penguins were anesthetized, intubated, and ventilated at a constant respiratory rate and different tidal volumes (VT). PO2 and PCO2 were measured in arterial blood and end-expired, mixed-expired, interclavicular air sac, and caudal thoracic air sac gas. Interclavicular air sac and end-expired gas had similar compositions. Caudal thoracic air sac gas was intermediate in composition to end-expired and inspired gas, and its PCO2 was 1.5-3.5 times greater than the value predicted from reinhaled dead space. This difference between measured and predicted caudal thoracic air sac PCO2 increased with VT but showed no relationship to changes in dead space-to-VT ratio. The difference is not explained by stratification or diffusive gas exchange across air sac walls. The results can be explained by postulating that inspired gas passes over exchange surfaces on its path to caudal air sacs. This is unexpected in the purely paleopulmonic lungs of penguins and suggests that airflow may not be caudocranial in all paleopulmonic parabronchi.

We studied discharge frequencies of 12 intrapulmonary chemoreceptors in the paleopulmonic lung of an emu (Dromiceius novaechollandiae) during unidirectional, artificial ventilation when step changes and static CO2 concentrations were given. Discharge frequency in afferent neurons from the receptors increased as intrapulmonary CO2 decreased. The response of the receptors to various static intrapulmonary CO2 concentrations was similar to that previously demonstrated for the duck and chicken. The median sensitivity of the emu receptors at one-half maximal discharge was 4.6 imp-(sec-0.01 F1CO2)-1. Discharge frequencies altered phasically in nine of 12 receptors when step changes in CO2 of 3.3% at 1.6 Hz were given in the unidirectional gas stream while four of 12 modulated their discharge when the CO2 changes were as rapid as 3.2 Hz. Hence, some receptors can respond to rapid fluctuations in CO2 in their microencironment. We conclude that intrapulmonary chemoreceptors in the paleopulmonic lung of the emu exhibit similar characteristics to those in birds that possess varying amounts of neopulmonic parabronchi, such as the duck and chicken.