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PubMed1990

Hormonal and renal responses to arterial chemoreceptor stimulation by almitrine in healthy and normotensive men.

Healthy and normotensive men (n = 11) were hospitalized and kept under controlled fluid and sodium intake (120 mequ/d) for 5 days. Their systemic arterial blood pressures as well as heart and breathing rates were measured, and venous blood and urine samples were collected at intervals of 1-4 h. Diuresis was induced by scheduled drinking of tea (150 ml/h). Electrolytes, osmolality, and creatinine were determined in both plasma and urine samples. Aldosterone, cortisol, and vasopressin concentrations were measured only in the plasma. On the 2nd and 3rd day of the experiments the participants received orally either a placebo-pill or 100 mg almitrine bismesylate (Vectarion). Each subject was tested in a placebo- and an almitrine experiment. The subjects responded to the almitrine treatment with a suppression of the plasma aldosterone content, a transient rise of glomerular filtration rate, a natriuresis and an increase of renal concentrating ability. In the placebo-experiments, only the transient rise of filtration rate was significant. The data indicate that almitrine, by stimulating the peripheral arterial chemoreceptors, suppresses plasma aldosterone and inhibits renal proximal sodium reabsorption by so far unknown mechanisms. They also suggest that oral and intravenous almitrine administrations, respectively, might differently affect renal hemodynamics and excretory function.

Adult↗

PubMed1990

Hypoxia and electrocortical activity in the fetal lamb: effects of brainstem transection and chemoreceptor denervation.

In order to investigate possible mechanisms for the effect of hypoxia on fetal electrocortical (ECoG) activity, the effects of 30 min of isocapnic hypoxia on ECoG were studied in three groups of unanaesthetized late-gestation fetal lambs in utero. One group was intact, in the second the brainstem was transected between the colliculi, and in the third the carotid sinus nerves and cervical vagosympathetic trunks were cut bilaterally to denervate the systemic arterial chemoreceptors. The incidence of high voltage (HV) ECoG activity was lower in brainstem-transected fetuses than in the other groups. All three groups showed an increased number of changes from low to high voltage and an increase in the incidence of HV activity at the onset of hypoxia, but the increases reached statistical significance only in the brainstem-transected group. It is concluded that the onset of hypoxia is often associated with an increase in HV ECoG activity, with the most consistent changes occurring after brainstem transection and similar but smaller increases in intact and denervated fetuses. Thus the response of fetal electrocortical activity to the onset of hypoxia does not depend on intact connections with the lower brainstem. However, the effect of hypoxia on fetal ECoG is minor and inconsistent and may be physiologically unimportant.

Animals↗

PubMed1990

[Chemoreceptor modulation of the respiratory reactions during muscle contractions in the cat].

Phasic contractions of the hindlimb muscles were induced in hypercapnia, hypoxia and hyperoxia. Absolute value of the lung ventilation and its kinetics depended on hypoxic and hypercapnic stimuli, reaching its maximum in their combination. Hypoxic stimulus decreased an increment of the lung ventilation and decelerated the latter's development. The interaction seems to be realized by neuronal mechanisms of dorsal respiratory nucleus. The latter is believed to play a major role in the mechanism of generation of central inspiratory activity based on respective chemoreceptor and proprioceptor afferent information.

Animals↗

PubMed1978

[Analysis of the mechanism of action of carbonic acid on tissue chemoreceptors].

Perfusion of the small intestine of anesthetized cats with a solution imitating metabolic acidosis (pH = 7.3; [HCO-3] = =20.2 mM; PCO2 = 38 mm Hg) produced a threshold reflex increase in the blood pressure. The subsequent decrease of [HCO-3] to 3.2 mM and pH to 6.5 evoked a gradual raise of the blood pressure followed by a sharp increase of pressor reflexes amplitude within the range of pH 6.5--6.3. Solutions imitating metabolic acidosis (pH = 7.1; [HCO-3] = 12.7 mM) were found to increase the concentration of H+ ions in the outflow perfusate and blood pressure to larger extent than solutions imitating respiratory acidosis (pH = 7.1; PCO2 = 75 mm Hg). If the solution pH was held constantly at 7.4 by simultaneous decreasing PCO2 and [HCO-3] by a factor of two, a reflex increase in the blood pressure and decrease of perfusate pH had no effect either on blood pressure or perfusate pH. The data obtained suggest that one of the primary determinants of different responses of the tissue chemoreceptors to CO2 is the interstitial pH.

Acid-Base Imbalance↗

PubMed1989

[Coronary chemoreceptors in rabbits].

Position and structure of the coronary ++chemoreceptor (CH) have been studied in 40 Chinchilla rabbits by means of neurohistological and histochemical methods. The CH is situated in the adventitia of the left coronary artery. The CH together with chromaffin cells includes blood vessels, small nervous fasciculi and connective tissue. According to luminescent intensity 2 groups of cells are distinguished. Two types of CH cells are revealed morphometrically, they differ in their size. Metachromasia at staining with toluidine++ blue demonstrates presence of serotonin in the CH. A possible role of the CH in pathogenesis of a sudden death is considered.

Animals↗

PubMed1985

Purification and characterization of the aspartate chemoreceptor.

The chemoreceptor for aspartate in Salmonella typhimurium was purified from an Escherichia coli strain containing a plasmid bearing the receptor's structural gene (tar). The receptor was solubilized from salt-washed membranes with the nonionic detergent octyl-beta-D-glucopyranoside and purified by a combination of ion exchange, molecular sieve and hydroxyapatite-agarose chromatography. The inclusion of glycerol and 1,10-phenanthroline in all buffers used prior to ion exchange chromatography prevented scission of the receptor by an endogenous proteolytic activity. The solubilized receptor was estimated to have a molecular weight of 248,000 from its behavior on Sephacryl S-300, suggesting that the receptor may be organized as a multimer containing 4 +/- 1 identical subunits. Circular dichroic measurements of the purified protein indicate that 78% of its residues are arranged in helical secondary structures.

Bacterial Proteins↗

PubMed1988

Environmental overheating as a cause of transient respiratory chemoreceptor dysfunction in an infant.

A central hypoventilatory state developed in a 6-month-old boy with environmentally induced hyperthermia. The condition subsided within 24 hours of mechanical ventilation. Hypoxic and hypercapneic challenges performed 2 weeks later showed complete resolution of the respiratory chemoreceptor dysfunction. The damage to the CNS caused by accidental hyperthermia in general, and more specifically to the respiratory center, and its possible etiologic role in the pathophysiology of sudden infant death syndrome are discussed.

Chemoreceptor Cells↗

PubMed1988

Well-maintained reflex responses of sympathetic nerve activity to stimulation of baroreceptor, chemoreceptor and cutaneous mechanoreceptors in neonatal capsaicin-treated rats.

Neonatal treatment with capsaicin (CAP) reduced the content of substance P-like immunoreactivity in the area of the nucleus tractus solitarii and the dorsal horn of the spinal cord in rats. The resting values of the mean arterial blood pressure and heart rate of CAP-treated rats were not significantly different from those of control rats. Reflex responses of the renal sympathetic nerve activity to stimulation of baroreceptor, chemoreceptor and cutaneous mechanoreceptor were compared in CAP- and vehicle-treated rats. Under these conditions the reflex responses were quite well maintained in CAP-treated rats.

Animals↗

PubMed1976

[Responses of small intestine tissue chemoreceptors to change in the pCO2, pH and (HCO3-) in perfusion solutions].

Perfusion of the small intestine of anesthetized cats with a solution having excessive CO2 and H+ concentration (pCO2 60 mm Hg; pH; 7.2; [HCO3-] 25 MM) produced a threshold reflex increase in the blood pressure. The subsequent increase of pCO2 to 380 mm Hg and decrease of pH to 6.4 evoked a gradual raise of the blood pressure (8.0+/-0.6 mm Hg) followed by the sharp increase of pressor reflexes amplitude within the range of pH 6.4--6.1. Tissue receptors were found to be essentially sensitive to solutions imitating metabolic acidosis (decrease of [HCO3-] within the physiological range of pH changes (pH 7.1--6.8). Solutions with pH 6.4--6.1 imitating respiratory acidosis (increase of pCO2) were more effective than those imitating metabolic acidosis. The possible role of interstitial pH changes in responses of the tissue chemoreceptors to CO2, is discussed.

Animals↗

PubMed1987

Renal hemodynamics and excretory function of healthy young men during stimulation of their peripheral arterial chemoreceptors by almitrine bismesylate.

Renal hemodynamics and excretory function were studied using clearance-techniques in 13 healthy, normotensive, normoxic young men undergoing moderate osmotic diuresis. Each subject was measured in two experiments both lasting from 7:30 a.m. to 6:00 p.m. In one of them 50 mg almitrine bismesylate (Vectarion) was ingested at 12:00 o'clock, whereas the other test served as control. There were only negligible changes of the parameters measured in the control experiments. Immediately after ingestion of the drug a renal vasodilation occurred, but 2-3 h later renal hemodynamic resistance tended to increase. Urinary sodium excretion rose after administration of almitrine. Initially this increase seemed to be caused by the kidney vasodilation but between the 3rd and 6th hour after giving the agent a natriuresis occurred that resulted from inhibition of renal tubular sodium reabsorption. The maximum of this renal tubular response was apparently not reached at the end of the experiments, i.e. 6 h after oral administration of the drug. Almitrine did not increase the renal potassium excretion. The data indicate that pharmacological stimulation of the peripheral arterial chemoreceptors by almitrine bismesylate in normoxic healthy humans causes reflectorically a slight renal vasoconstriction and a long-lasting inhibition of renal tubular sodium reabsorption. These findings are in good agreement with previously published data obtained in animal experiments.

Adult↗

PubMed1987

Plasma vasopressin levels in healthy young men in response to stimulation of the peripheral arterial chemoreceptors by almitrine bismesylate.

The plasma arginine vasopressin (AVP) concentration, the plasma osmolality as well as the systemic arterial blood pressure, the heart rate, and the minute ventilation were determined in four healthy, normotensive, normoxic young men undergoing moderate osmotic diuresis. Each subject was measured in two experiments, both lasting from 7:30 a.m. to 6:00 p.m.. In one of them they obtained 50 mg almitrine bismesylate (Vectarion) at 12:00 o'clock, whereas the other test served as control experiment. There were only negligible changes of the parameters measured in the control experiments and also only weak responses of the cardiorespiratory values in the almitrine treated group. Compared with the data obtained 30 min before administration of the drug, measurements carried out 90 min after the ingestion showed a decrease of plasma AVP in all four subjects through plasma osmolality was increased in three of the four cases. A comparison of the mean values of all data obtained in the morning, i.e. before the oral administration of the drug, with those determined in the afternoon revealed that three out of four subjects had responded to almitrine with a fall of plasma AVP regardless of an increase of plasma osmolality in all these three cases. One person did not react to almitrine ingestion, neither with plasma AVP nor with plasma osmolality. In the control experiments the corresponding reaction pattern was uncharacteristic. The data do not support the assumption that arterial chemoreceptor stimulation increases plasma AVP. They rather indicate that excitation of these pO2-sensors in normoxic humans suppresses plasma AVP by mechanisms so far unknown.

Adult↗

PubMed1985

Chemoreception in the sea: adaptations of chemoreceptors and behaviour to aquatic stimulus conditions.

The chemical stimulus environment is pulsed in nature. Mixtures can identify an odour source with great specificity, and (hence) most chemical signals are mixtures, even when initial research may seem to indicate that single compounds are sufficient to release complete behaviour. Information currents are often necessary to receive chemical stimuli. Receptor cell physiology reflects the microenvironment in which the receptor organ operates. Receptor cells interface with the stimulus environment in such a way as to enhance signal-to-noise ratios and to cover the naturally occurring dynamic stimulus range. Different chemoreceptor organs are designed to perform a number of different behavioural tasks. This is equally true for aquatic species that sample one (aqueous) medium as for terrestrial species that sample air and aqueous media. Hence, most of these principles are not unique to aquatic chemoreception.

Acetylcholine↗

PubMed1979

Peripheral chemoreceptors and exercise hyperpnea.

The carotid bodies appear to be the only peripheral chemoreceptors mediating ventilatory control during exercise in man. While little is known about the mechanism of stimulation, much is known about the effects of carotid body stimulation upon pulmonary ventilation (VE). These effects have been produced by hypercapnia, hypoxia, metabolic acidosis, arterial blood pressure, temperature, and catecholamines. A signal from CO2 flow is attractive because of the strong correlation between CO2 output and VE during exercise. The carotid body's role in the hyperpnea depends on the intensity of exercise. During heavy exercise, pH falls and hyperventilation ensues. The carotid bodies appear to be the exclusive mediators of the ventilatory compensation for the acidosis at this exercise intensity. For moderate exercise, mean arterial PCO2 does not change. Therefore, how is the CO2 signal transmitted to the respiratory center? Two current theories are: (1) since arterial PCO2 and pH oscillate with each breath, the amplitude and period of these oscillations may change during exercise and may be of sufficient magnitude to stimulate the carotid bodies, and (2) there exists a disequilibrium between hydrogen ion activity within the red blood cell and in the plasma because carbonic anhydrase is found in the former but not the latter. This theory assumes that the enzyme is not accessible to the plasma.

Aortic Bodies↗

PubMedDate not supplied

[Chemoreceptor function and metabolism of the carotid body in the rat].

Using fluorimetric and polarographic determination of cell respiration, metabolic reactions of the carotid body of rats to adequate stimulation have been revealed. Functional relationships of the dose--effect type, which were found for these reactions, may be approximated by equations which are similar to those describing the unconditioned reflexes from the carotid chemoreceptors. However, reactions of the metabolics systems of the carotid body account for the perception of not all chemical stimuli, but only of acids and some alkaloids. These data reveal the heteregeneity of the carotid chemosensory system not only in the amphibians (which was known earlier), but in mammals as well.

Animals↗

PubMed1983

Chemoreceptor sensitivity in adaptation to high altitude.

Studies were carried out in a group of 20 young male subjects to investigate the changes in chemoreceptor sensitivity during acclimatization to altitude. Their hypoxic sensitivity and carbon dioxide sensitivity were studied at Delhi, during acclimatization at 3500 m, and on return to sea level. Similar studies were also done in a group of 10 acclimatized lowlanders who stayed at 3500-4000 m for 12-14 months, and also on 10 high-altitude natives. The results showed no significant alteration in the hypoxic sensitivity of the lowlanders; but CO2 sensitivity was markedly elevated at altitude, both in sojourners and acclimatized lowlanders. The high-altitude natives showed less sensitivity to hypoxia, whereas the CO2 sensitivity was normal.

Acclimatization↗

PubMed1983

Respiratory neurones in the chemoreceptor pathway activated by almitrine bismesylate.

In anaesthetized, paralysed and artificially ventilated dogs, activities were recorded from the phrenic nerve and from respiratory units within the nucleus tractus solitarius (NTS) and the nucleus ambiguus (NA). Prolonged stimulation of peripheral chemoreceptors by almitrine (50 micrograms X kg-1 i.v.) induced an increase in the firing rate of the R alpha and R beta inspiratory neurones of the NTS. Some expiratory neurones were found in the NTS and their firing rate was also enhanced by almitrine. In the NA, the respiratory neurones have active phase-firing patterns that can be quite different: the late peak inspiratory or expiratory neurones have linearly augmenting discharges with a steeper cessation. In contrast the early burst inspiratory or expiratory units start to fire with the onset of their active phase, rapidly achieve peak firing frequency and then the firing frequency declines through the remainder of the active phase. Almitrine had been found to activate these neurones particularly the expiratory neurones of the N.A.

Almitrine↗

PubMed1981

[Importance of chemoreceptor stimuli to the speed of switching the respiratory response to exertion on and off].

The magnitude of the exercise respiratory response and its switch on and switch off rates were studied in 12 normal men breathing different gas mixtures. It was shown that hypercapnic stimulus reinforced and accelerated the respiratory response to exercise. Hypoxic stimulus mostly resulted in the increased though transient changes in the ventilatory rate at the start and at the end of exercise. This effect seems likely to be mediated by the fast-responding arterial chemoreceptors.

Adult↗

PubMed1982

[Recovery of colchicine-blocked chemoreceptor reactions of the frog tongue as affected by electrical stimulation of the sympathetic nervous system].

Under adequate stimulation of tongue chemoreceptors with feeds synchronous recording of the total afferent impulse activity of the glossal branches of Rana temporaria glossopharyngeal nerves was used to demonstrate the facilitation effect of electric stimulation of the I sympathetic ganglion on the receptor reactions in health and after treatment with colchicine provoking a considerable weakening of the reactions. The data are discussed in the light of the adaptation-trophic effect of the sympathetic system at the level of molecular-metabolic intracellular processes. No poisoning effect of alkaloid on the sympathetic fibers has been recorded.

Animals↗