Cardioprotective and vasomotor effects of HO activity during acute and chronic hypoxia

Prolonged hypoxia leads to the development of pulmonary hypertension. Recent reports have suggested enhancement of heme oxygenase (HO), the major source of intracellular carbon monoxide (CO), prevents hypoxia-induced pulmonary hypertension and vascular remodeling in rats. Therefore, we hypothesized that inhibition of HO activity by tin protoporphyrin (SnPP) would exacerbate the development of pulmonary hypertension. Rats were injected weekly with either saline or SnPP (50 micromol/kg) and exposed to hypobaric hypoxia or room air for 5 wk. Pulmonary and carotid arteries were catheterized, and animals were allowed to recover for 48 h. Pulmonary and systemic pressures, along with cardiac output, were recorded during room air and acute 10% O2 breathing in conscious rats. No difference was detected in pulmonary artery pressure between saline- and SnPP-treated animals in either normoxic or hypoxic groups. However, blockade of HO activity altered both systemic and pulmonary vasoreactivity to acute hypoxic challenge. Despite no change in baseline pulmonary artery pressure, all rats treated with SnPP had decreased ratio of right ventricular (RV) weight to left ventricular (LV) plus septal (S) weight (RV/LV + S) compared with saline-treated animals. Echocardiograms suggested dilatation of the RV and decreased RV function in hypoxic SnPP-treated rats. Together these data suggest that inhibition of HO activity and CO production does not exacerbate pulmonary hypertension, but rather that HO and CO may be involved in mediating pulmonary and systemic vasoreactivity to acute hypoxia and hypoxia-induced RV function.     

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.     

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.     

Changes in conditioned reflex activity during adaptation of the rat to pressure-chamber and high-altitude hypoxia

A group of rats with a stereotype of conditioned reflexes was preliminarily trained to hypoxia effects during 30 days (at the "altitude" of 6000 m, time of exhibition--from 10 to 60 min, for 18 days--only 60 min). Adaptive changes in the process of training consisted in a weakening of differentiation inhibition, partial amnesia of the conditioned reaction of active avoidance and appearance of phasic states (equalization and paradoxical phases) in the cerebral cortex. The following adaptation of hypoxia "trained" rats to new natural conditions of Alpine altitude (3200 m) proceeded favourably, without disturbance of differentiation inhibition and without phasic states. Rats without preliminary training to altitude chamber hypoxia, in mountains (3200 m) were subjected to moderate tension resulting in protective inhibition, partial amnesia and transient disturbance of differentiation inhibition.     

Responses of bulbospinal neurons during expiration reflex in cats

The responses of 129 bulbospinal (BS) neurons were investigated an anesthetized cats during the expiration reflex evoked by mechanical stimulation of the vocal folds or electrostimulation of the superior laryngeal nerve. It was found that in addition to expiratory and inspiratory neurons, a large number of nonrespiratory BS cells localized bilaterially, primarily in the giant-cell tegmental fields, are activated. It is shown that expulsive expiration during this reflex is to a considerable extent provided by activation of non-respiratory BS neurons participating also in the transmission of descending influences from high-threshold afferents of other modalities.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 1, pp. 88–98, January–February, 1991.     

Activity of propriospinal neurons during the scratch reflex in cats

Fictitious scratching, i.e., rhythmic activity of hind-limb motoneurons at the characteristic scratching frequency, was evoked by tactile stimulation of the ear in thalamic cats immobilized with flaxedil. Activity of propriospinal neurons in segments C₁, C₂, and T₄–T₇ was recorded extracellularly. The neurons were identified by their antidromic response to stimulation of their axons in segment L₁. Most neurons did not respond to stimulation of the ear. Some neurons, however, were activated during fictitious scratching. Neurons of the cervical segments responded not only to stimulation of the ear, but also to tactile stimulation of the forelimbs and also to passive movements of those limbs. Neurons of the thoracic segments were activated only by stimulation of the ipsilateral ear; these neurons were inhibited by stimulation of the contralateral ear. The role of the propriospinal neurons in the activation of the spinal mechanisms of scratching is discussed.Institute for Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 9, No. 5, pp. 504–511, September–October, 1977.     

Changes in tissue monoamine oxidase activity and resistance to acute hypoxia in rats during stress

Male Wistar rats exposed to different stresses developed shifts in the brain and liver monoaminoxidase activity. In the so called "cognitive" stimulation, the activity was enhanced in the brain and reduced in liver. Mild stresses also enhanced the activity in the brain. Extreme stimulation (starch peritonitis) caused a significant diminishing of the activity in the brain. All the stress schedules accompanied by enhancement of the brain monoaminoxidase activity increased the rats' tolerance of acute hypoxic hypoxia. Negative correlations between the blood lactic acid contents and the brain monoaminoxidase activity were revealed in rats of both the control and the "cognitive" groups. The findings suggest a direct interrelationship between post-stress shifts of the brain monoaminoxidase activity and the hypoxia tolerance.     

Self-limiting reflex luteinizing hormone release and sexual behavior during extended periods of unrestricted copulatory activity in estrous domestic cats

Estrous female cats (queens) were permitted 36-h periods of unrestricted mating activity; they then were injected with various doses of gonadotropin-releasing hormone (GnRH) at 36 h and allowed single copulations at 48 or 72 h of study. Serum luteinizing hormone (LH) levels were determined in samples collected prior to and 2 h after the initial copulation, before and 30 min after selected copulations during the next 10 h, and before and 30 min after copulations occurring at 20-24, 36, and 48-72 h, as well as 0, 15, and 30 min after the GnRH injections (0.3-3.0 micrograms/kg) at 36 h of study. Copulations occurred 14-20 times in 12 h and 20-36 times in 36 h. Copulation frequency (mean +/- SEM) decreased (p less than 0.05) from 5.5 +/- 0.6/2 h initially to 1.5 +/- 0.6/2 h during the subsequent 2-h period, and was 1.4 +/- 0.2/2 h at 12-36 h of study. Intromissions lasted 1-27 (8 +/- 0.3) s. Variation in durations of mounting by males (1.7 +/- 0.1 min; range, 0.3-10 min) or of the postcoital behavioral reactions displayed by the queens (2.5 +/- 0.1 min; range, 1-17 min) could not be related to animals or time of study. Peak serum LH levels (11-280 ng/ml; mean, 112 +/- 30 ng/ml) were observed at 2-4 h after the first mating. Mean LH steadily declined thereafter, reached basal values (less than or equal to 3 ng/ml) by 20-24 h, and remained low at 36 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

The correlations of the evoked activity of the auditory cortex and amygdala in cats during conditioned reflex activities]

By averaged summary activity of symmetric points of the cat auditory cortex and amygdala evoked by sound, the character of interaction (Spirman coefficient of correlation) was determined between the structures before, at elaboration, at extinction and restoration of instrumental food-procuring reflex and also at automatization of the reflex. Individual character of co-tuning of the cortex and amygdala was found at adaptation of the animal, changing into close interconnections at formation of the reflex and into disturbance of their correlation at its extinction. Stabilization of the reflex up to the stage of automatization was accompanied by the weakening of connections between the cortex and amygdala. The results testify to complex and dynamic character of interaction in the system cortex-amygdala in conditioned activity.