Carotid chemoreceptor activity during acute and sustained hypoxia in goats

The role of carotid body chemoreceptors in ventilatory acclimatization to hypoxia, i.e., the progressive, time-dependent increase in ventilation during the first several hours or days of hypoxic exposure, is not well understood. The purpose of this investigation was to characterize the effects of acute and prolonged (up to 4 h) hypoxia on carotid body chemoreceptor discharge frequency in anesthetized goats. The goat was chosen for study because of its well-documented and rapid acclimatization to hypoxia. The response of the goat carotid body to acute progressive isocapnic hypoxia was similar to other species, i.e., a hyperbolic increase in discharge as arterial PO2 (PaO2) decreased. The response of 35 single chemoreceptor fibers to an isocapnic [arterial PCO2 (PaCO2) 38-40 Torr)] decrease in PaO2 of from 100 +/- 1.7 to 40.7 +/- 0.5 (SE) Torr was an increase in mean discharge frequency from 1.7 +/- 0.2 to 5.8 +/- 0.4 impulses. During sustained isocapnic steady-state hypoxia (PaO2 39.8 +/- 0.5 Torr, PaCO2, 38.4 +/- 0.4 Torr) chemoreceptor afferent discharge frequency remained constant for the first hour of hypoxic exposure. Thereafter, single-fiber chemoreceptor afferents exhibited a progressive, time-related increase in discharge (1.3 +/- 0.2 impulses.s-1.h-1, P less than 0.01) during sustained hypoxia of up to 4-h duration. These data suggest that increased carotid chemoreceptor activity contributes to ventilatory acclimatization to hypoxia.     

Decay of inspiratory muscle pressure during expiration in anesthetized cats

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg) we studied the antagonistic pressure developed by the inspiratory muscles during expiration (PmusI). This was accomplished in two ways: 1) with our previously reported method (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 1266-1271, 1982) based on the measurement of changes in lung volume and airflow during spontaneous expiration, together with determination of the total passive respiratory system elastance and resistance; and 2) measurement of the time course of changes in tracheal/pressure after airway occlusion at end inspiration, up to the moment when the inspiratory muscles become completely relaxed. The agreement between the two methods is generally good, both in the amplitude of PmusI and in its time course. We also applied the first method to spontaneous expirations through added linear resistive loads. These did not alter the relative decay of PmusI. Thus in anesthetized cats the braking action of the inspiratory muscles does not decrease when expiratory resistive loads are added, i.e., when such braking is clearly not required.     

Urethral closure mechanisms during sneezing-induced stress in anesthetized female cats

During stress-induced increase in abdominal pressure, urinary continence is maintained by urethral closure mechanisms. Active urethral response has been studied in dogs and rats. Such an active urethral response is also believed to occur in humans during stress events. We aimed to investigate urethral closure mechanisms during sneezing in cats. Urethral pressures along the urethra (UP1-UP4), with microtip transducer catheters with UP4 positioned in the distal urethra where the external urethral sphincter (EUS) is located, and intravesical pressure were measured, and abdominal wall, anal sphincter (AS), levator ani (LA), and EUS electromyograms (EMGs) were recorded during sneezing under closed-abdomen and open-abdomen conditions in eight anesthetized adult female cats. Proximal and middle urethral response induced by sneezing was not different from bladder response. Distal urethral response was greater compared with proximal and middle urethral and bladder response. In the open-abdomen bladder, proximal and middle urethral responses were similarly decreased and distal urethral response was unchanged compared with the closed-abdomen bladder. Bladder and urethral responses were positively correlated to sneeze strength. EUS, LA, and AS EMGs increased during sneezing. No urine leakage was observed, regardless of the strength of sneeze. In cats urethral closure mechanisms are partly passive in the proximal and middle urethra and involve an active component in the distal urethra that is believed to result from EUS and possibly LA contractions. Because central serotonin exerts similar effects on the lower urinary tract in cats and humans, the cat may represent a relevant model for pharmacological studies on continence mechanisms.     

Selective metabolic effects of salbutamol in anesthetized cats.

Salbutamol was found to produce a selective stimulation of beta adrenergic receptors mediating metabolic responses in anesthesized cats. Salbutamol was infused intravenously at a rate of 1 μg/Kg/min; this agent produced a significant decrease in diastolic blood pressure and concomitantly increased blood glucose and lactate while decreasing plasma potassium. Salbutamol did not elevate plasma free fatty acids. In contrast to salbutamol, comparable infusions of isoproterenol produced all cardiovascular and metabolic effects non-selectively. The cardiovascular and metabolic effects of salbutamol were blocked by oxprenolol, a beta adrenergic receptor antagonist. The apparent selectivity of action of salbutamol suggests that metabolic beta adrenergic receptors are heterogeneous and can be differentiated into at least two separate types.     

Cardiac sympathetic afferent stimulation augments the arterial chemoreceptor reflex in anesthetized rats.

Chronic heart failure (CHF) is well known to be associated with both an enhanced chemoreceptor reflex and an augmented cardiac "sympathetic afferent reflex" (CSAR). The augmentation of the CSAR may play an important role in the enhanced chemoreceptor reflex in the CHF state because the same central areas are involved in the sympathetic outputs of both reflexes. We determined whether chemical and electrical stimulation of the CSAR augments chemoreceptor reflex function in normal rats. Under anesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. The chemoreceptor reflex was tested by unilateral intra-carotid artery bolus injection of potassium cyanide (KCN) and nicotine. We found that 1) left ventricular epicardial application of capsaicin increased the pressor responses and the RSNA responses to chemoreflex activation induced by both KCN and nicotine; 2) when the central end of the left cardiac sympathetic nerve was electrically stimulated, both the pressor and the RSNA responses to chemoreflex activation induced by KCN were increased; 3) pretreatment with intracerebroventricular injection of losartan (500 nmol) completely prevented the enhanced chemoreceptor reflex induced by electrical stimulation of the cardiac sympathetic nerve; and 4) bilateral microinjection of losartan (250 pmol) into the nucleus tractus solitarii (NTS) completely abolished the enhanced chemoreceptor reflex by epicardial application of capsaicin. These results suggest that both the chemical and electrical stimulation of the CSAR augments chemoreceptor reflex and that central ANG II, specially located in the NTS, plays a major role in these reflex interactions.     

Efferent activity in the phrenic nerve during startle reflex in chloralose anesthetized cats

Efferent activity was investigated in the phrenic nerve during startle reflex manifesting as somatic nerve discharges (lower intercostal nerves and the nerve endings) in chloralose anesthetized cats. Inhibition (usually of short duration, lasting 23–36 msec) of inspiration activity was found to be the main component of response in the phrenic nerve in the shaping of "low threshold" startle reflex produced by acoustic and tactile stimuli and stimulation of low threshold peripheral afferents. Reflex discharge prevailed amongst the response patterns produced in the phrenic nerve by stimulating high threshold afferents, i.e., early (propriospinal) and late (suprasegmental, arising from stimulating intercostal nerve) or late only (when stimulating the hindlimb nerves). Two patterns of late response could be distinguished, one on inspiration (found in roughly 3 out of 4 experiments) and other on exhalation — the respiratory homologs of somatic startle reflex. Response pattern is described throughout the respiratory cycle. Structure and respiratory modulation of reflex responses produced in the phrenic nerve by stimulating bulbar respiratory structure are also examined. Possible neurophysiological mechanisms underlying phrenic response during the shaping of startle reflex are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 4, pp. 473–482, July–August, 1987.     

Chronic hypoxia enhances the phrenic nerve response to arterial chemoreceptor stimulation in anesthetized rats.

Chronic exposure to hypoxia results in a time-dependent increase in ventilation called ventilatory acclimatization to hypoxia. Increased O(2) sensitivity of arterial chemoreceptors contributes to ventilatory acclimatization to hypoxia, but other mechanisms have also been hypothesized. We designed this experiment to determine whether central nervous system processing of peripheral chemoreceptor input is affected by chronic hypoxic exposure. The carotid sinus nerve was stimulated supramaximally at different frequencies (0.5-20 Hz, 0.2-ms duration) during recording of phrenic nerve activity in two groups of anesthetized, ventilated, vagotomized rats. In the chronically hypoxic group (7 days at 80 Torr inspired PO(2)), phrenic burst frequency (f(R), bursts/min) was significantly higher than in the normoxic control group with carotid sinus nerve stimulation frequencies >5 Hz. In the chronically hypoxic group, peak amplitude of integrated phrenic nerve activity ( integral Phr, percent baseline) or change in integral Phr was significantly greater at stimulation frequencies between 5 and 17 Hz, and minute phrenic activity ( integral Phr x f(R)) was significantly greater at stimulation frequencies >5 Hz. These experiments show that chronic hypoxia facilitates the translation of arterial chemoreceptor afferent input to ventilatory efferent output through a mechanism in the central nervous system.     

Synaptic excitation of reticulospinal neurons during the startle reaction in cats anesthetized with chloralose

Synaptic processes in reticulospinal neurons of the pons and medulla during the startle reaction evoked by somatic stimulation were investigated in cats anesthetized with chloralose. The main type of response of reticulospinalneurons was found to be PSPs involving intrareticular (proprioreticular) pathways of varied complexity: oligosynaptic (including supposedly monosynaptic) and polysynaptic. Comparison of EPSP characteristics with parameters of spino-bulbospinal (SBS) discharges recorded simultaneously in the intercostal nerves showed that polysynaptic EPSPs evoked through corresponding proprioreticular pathways were most effective in creating a descending SBS volley. About half the reticulospinal neurons of the pons and medulla were involved at any one time in the synaptic relay process during the startle reflex. The conduction velocity in axons of these neurons varied from 30 to 98 m/sec (means 64.5 Mp 16.5 m/sec). Some distinguishing features of the functional organization of the reticular "center" for the startle reaction are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 6, pp. 594–603, November–December, 1981.     

Lesions in retrotrapezoid nucleus decrease ventilatory output in anesthetized or decerebrate cats.

Kainic acid (KA) injections into the retrotrapezoid nucleus (RTN) of anesthetized deafferented cats profoundly decreased phrenic activity (PA) and CO2 sensitivity (J. Appl. Physiol. 68: 1157-1166, 1990). In this study small electrolytic lesions of the RTN produced the same results, indicating that the KA destroyed cells. We then asked whether anesthetic depression or the absence of peripheral chemoreceptors could explain the degree of respiratory depression observed. In decerebrate cats electrolytic lesions of the RTN resulted in a decrease in PA similar to that seen under anesthesia. CO2 sensitivity was decreased by RTN lesions that extended into the caudal RTN but less so than under anesthesia. KA injections resulted in an initial increase in PA followed by a continuous decrease, a pattern similar to that seen under anesthesia but with a slower time course. CO2 sensitivity was essentially absent. Peripheral chemodenervation produced a small further decrease in PA and a downward shift of the CO2 response without change in slope. Blood pressure was unaffected by RTN lesions but was decreased by more-caudal lesions without respiratory effects. The RTN appears to be necessary for the maintenance of eupneic phrenic activity and CO2 sensitivity even in decerebrate cats with intact peripheral chemoreceptors.     

Carotid and cardiopulmonary chemoreceptor activity increases hippocampal theta rhythm in conscious rabbits

We have examined whether activation of carotid artery chemoreceptors causes alerting in conscious rabbits. Injection of phenylbiguanide (a 5-hydroxytryptamine(3)-receptor agonist) into the common carotid artery of conscious rabbits increased the proportion of theta rhythm in the hippocampal EEG, commencing in the first 5-s epoch after the injection. Intravenous injection of phenylbiguanide also increased the proportion of theta rhythm in the hippocampal electroencephalogram (EEG), but the onset of the change was not until the second 5-s epoch following injection. Injection of Ringer solution, either into the common carotid artery or into the marginal ear vein, did not affect the hippocampal EEG. Results suggest that phenylbiguanide-mediated activation of carotid and cardiopulmonary chemoreceptor afferents alerts the animal, as assessed by induction of theta rhythm in the hippocampal EEG. This alerting response presumably reflects the action of neural inputs that enter the brain with the carotid sinus nerve at the level of the medulla oblongata.