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Biomedical subjects

S Lahiri

Publications and source records attributed to S Lahiri.

At least 109 records · Page 6Linked to original sources
PubMed1994

Carotid body chemoreception: mechanisms and dynamic protection against apnea.

A critical role of peripheral chemoreceptors in terminating apnea and in initiating normal breathing has been emphasized. Since these are the only organs which signal hypoxia, failure of its adequate development can contribute to the disease of respiratory failure in neonatal life. The failure may reside in any of the steps from initiation of O2 chemoreception involving respiratory and non-respiratory pigments, ion balance including H+ and Ca2+, neurotransmitter mechanisms and transduction.

Animals↗
PubMed1994

Antibody-induced alterations of protein and nucleic acid metabolism during experimental thyroglobulin immunization.

The protein and nucleic acid contents of liver, spleen, muscle, kidney, and brain were studied in experimental autoimmune thyroiditis. Protein and ribonucleic acid levels showed a positive increase in the case of liver, spleen, and muscle on days 56 and 98 after immunization and on day 147 they reached control levels. Spleen deoxyribonucleic acid showed a significant increase on day 56, whereas the other days showed no change. Kidney and brain tissue revealed no change.

Animals↗
PubMed1993

Hyperbaric oxygenation alters carotid body ultrastructure and function.

We previously demonstrated that chronic normobaric hyperoxia (NH) for 60-67 h attenuated the carotid chemosensory response to hypoxia, probably initiated by the generation of reactive oxygen species (ROS). Since biological systems are affected by oxygen in a dose-dependent manner, we hypothesized that hyperbaric oxygenation (HBO) would affect the cellular mechanisms of oxygen chemoreception in a shorter time. To test the hypothesis, we studied the effects of oxygen at 5 atmospheres absolute (ATA) on cats (n = 7) carotid body ultrastructure and chemosensory responses to hypoxia, hypercapnia, and to bolus injections of cyanide, nicotine and dopamine. Four control cats breathed room air at 1 ATA. At the termination of the experiments, carotid bodies from 4 cats in each group were fixed and prepared for electron microscopy and morphometry. On the average, HBO diminished the chemosensory responsiveness to hypoxia (P < 0.01, unpaired t-test) within about 2 h, supporting the hypothesis. The responses to hypercapnia or bolus injections of cyanide, nicotine and dopamine were normal. HBO did not diminish the distribution of the dense-cored vesicles but significantly increased the mean volume-density of mitochondria and decreased the cristated area per mitochondrion in the glomus cells. The latter suggests a link between oxidative metabolism and chemosensing, and the former excludes availability of neurotransmitters being the cause of the blunted chemosensory response to hypoxia.

Animals↗
PubMed1993

CO reveals dual mechanisms of O2 chemoreception in the cat carotid body.

The hypothesis that CO-binding pigments in the carotid body participate in O2 chemoreception was tested. The chemosensory nerve discharges of cat carotid body perfused and superfused in vitro at 36-37 degrees C with cell-free solution containing CO2-HCO3- (pH approximately equal to 7.39) were recorded to monitor O2 chemoreception. Several levels of PCO (60-550 Torr) at two levels of PO2 (50 Torr-140 Torr) were used. With high PCO of 500-550 Torr at any PO2 the discharge rate peaked promptly but the effect was significantly less than that to hypoxia. At any stage of the CO effect, exposure to light promptly attenuated or eliminated the response, as if the stimulatory effect of hypoxia was absent. Lower PCO of 60-70 Torr attenuated the response to hypoxia which was not suppressed by light. PCO of 140 Torr also attenuated the response to hypoxia and made the activity partially photolabile. During high PCO exposure the excitatory response to cyanide but not to nicotine was attenuated, consistent with the idea that the effects of nicotine are downstream from those of CO. Both inhibitory and excitatory effects of CO were promptly reversible. The results indicate that two types of CO-binding chromophores participate in O2 chemoreception in the carotid body.

Animals↗
PubMed1993

Differential modulation by extracellular ATP of carotid chemosensory responses.

The possibility that the carotid body has ATP surface receptors that mediate O2 chemoreception was tested. To distinguish between the event(s) initiating chemoreception and those at the neurotransmitter level, we also tested the chemosensory response to nicotine before and after ATP administration. Carotid bodies from cats anesthetized with pentobarbital sodium were perfused and superfused in vitro with modified Tyrode solution (PCO2 < 1 Torr, pH 7.4, 36 degrees C) equilibrated at PO2 > 400 or approximately 150 Torr while chemosensory discharge was recorded extracellularly. ATP and adenosine 5'-[gamma-thio]triphosphate stimulated discharge with similar dose dependence, whereas adenosine had little effect. ATP infusion for > or = 2 min evoked an initial stimulation of discharge followed by a decline to baseline (desensitization). Desensitization did not affect the response to hypoxia (perfusate flow interruption) but inhibited the response to nicotine (4-nmol pulse). Therefore, 1) the carotid body has surface ATP receptors that may mediate the chemosensory response to nicotine but not to hypoxia and 2) nicotinic receptors are not required for carotid body O2 chemoreception.

Adenosine↗
PubMed1993

Contribution of in vivo microvascular PO2 in the cat carotid body chemotransduction.

To understand the interplay between microcirculatory control and carotid body (CB) function, we simultaneously measured carotid body microvascular PO2 (CBM PO2) and chemosensory activity in the cat in vivo under several experimental conditions. Cats were anesthetized with pentobarbital sodium, paralyzed, and artificially ventilated. CBs were exposed, and steady-state CBM PO2 was measured by the O2-dependent quenching of the phosphorescence of Pd-meso-tetra-(4-carboxyphenyl)porphine, which was administered intravenously. A few fibers of the carotid sinus nerve were used to record chemosensory discharges. At arterial PO2 (PaO2) of 103.4 +/- 4.1 Torr, CBM PO2 was 52.5 +/- 3.6 Torr (n = 9). Graded lowering of PaO2 from 160 to 50 Torr resulted in nearly proportional decreases in CBM PO2, but at lower PaO2 the decrease in CBM PO2 became more substantial. As PaO2 decreased, chemosensory discharge increased in parallel with CBM PO2. Hypercapnia and hypocapnia did not significantly change the relationship between PaO2 and CBM PO2, although the chemosensory discharge responded significantly. CBM PO2 and chemosensory discharge were not affected by hemorrhagic hypotension until arterial blood pressure fell below approximately 50 Torr and then CBM PO2 decreased and chemosensory discharge increased. The lack of a significant effect of hemorrhagic hypotension indicated that O2 delivery to CB was almost independent of the systemic blood pressure. Taken together, the observations suggest that CB microcirculation and PO2 are subject to control by intrinsic mechanisms and that CBM PO2 is compatible with oxidative metabolism playing a role in O2 chemoreception during hypoxia.

Animals↗
PubMed1993

Dynamics of carotid body responses in vitro in the presence of CO2-HCO3-: role of carbonic anhydrase.

The role of carbonic anhydrase (CNA) in the dynamics of carotid body (CB) function was tested by studying the effects of the membrane-permeable CNA inhibitor methazolamide on the chemosensory responses of the cat CB, perfused and superfused in vitro with cell-free and modified Tyrode solution at 36.5 +/- 0.5 degrees C in the presence of CO2-HCO3- (PO2 = 120 Torr, PCO2 = 32 Torr, pH = 7.40). The bulk of CO2 flow to the CB from the external milieu was overwhelmingly large relative to the metabolic production of CO2 in the CB. Accordingly, the relative contribution of the endogenous CO2 to the CB responses was small. The chemosensory nerve discharges were recorded from the whole desheathed carotid sinus nerve. The responses to acidic hypercapnia (PCO2 = 50-60 Torr, pH = 7.20-7.10), hypoxia (PO2 = 25 and 50 Torr), perfusate flow interruption, and bolus injections of sodium cyanide (20-40 nmol) were tested. To contrast, we also measured the effects of nicotine (2-4 nmol), which may act at sites other than those for O2 and CO2. Methazolamide (30 mg/l) in the perfusate at constant PCO2 and pH reduced the baseline activity and delayed the responses to step changes in PCO2 (and concomitantly pH) and PO2 and to cyanide but not to nicotine. The steady-state responses to these stimuli, measured as differences from control, were reduced, but not significantly. The initial overshoots seen with step changes in both high PCO2 and low PO2 were eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of doxapram on carotid chemoreceptor activity in newborn kittens.

Doxapram is a respiratory stimulant which acts on peripheral chemoreceptors and central respiratory neurons in a dose-dependent fashion in the adult cat. In the newborn, the mechanisms of action of doxapram are still unclear. To evaluate the effects of doxapram on the carotid chemosensory discharge and its relationship with dopaminergic mechanisms in the carotid body, two groups of kittens less than 13 days old, anesthetized, artificially ventilated and paralyzed, were prepared for the recording of a single or a few chemosensory afferents of the carotid sinus nerve. The chemosensory activity was recorded under five conditions of inspired gas mixtures (21 and 8% O2 in N2, 100% O2, 5 and 10% CO2 in O2). Group 1 (n = 9) received only doxapram and group 2 (n = 8) was pretreated with haloperidol (1 mg/kg), a dopamine D2-receptor blocker, before receiving doxapram. Doxapram significantly stimulated the discharge rate of the carotid chemoafferents under all conditions of inspired gas. The chemosensory discharge was increased by haloperidol, and was raised further after doxapram by an amount similar to group 1. For instance, in normoxia, the activity increased from 2.9 +/- 0.4 to 7.5 +/- 0.9 impulse/s (mean +/- SEM, p < 0.01) in group 1 and from 3.8 +/- 0.6 to 9.1 +/- 1.0 impulse/s (p < 0.01) in group 2. These results indicate that the mechanisms of response of carotid chemoreceptor to doxapram are developed in the newborn kitten and doxapram acts independent of the dopaminergic mechanisms in the carotid body.

Animals↗
PubMed1993

Endothelin binding to receptors and endothelin production by human thyroid follicular cells: effects of transforming growth factor-beta and thyrotropin.

Measurable endothelin (ET) was found in serum-free medium of cultured primary thyroid cells derived from human thyroid tissues after 3 days incubation at levels ranging from undetectable to 35 fmol/100,000 cells. Out of 12 thyroid glands studied, 2 responded to transforming growth factor-beta (TGF-beta) treatment with increased ET secretion into medium. Detailed study of cells derived from one of these thyroids showed TGF-beta at 1 ng/ml stimulated ET secretion from 13.7 to 33.3 fmol/100,000 cells after 3 days incubation. Although TSH alone did not significantly modulate ET release into medium, TSH enhanced the stimulatory effect of TGF-beta. A combination of TSH at 1 mU/ml and TGF-beta at 1 ng/ml stimulated ET secretion to 63.8 fmol/100,000 cells after 3 days incubation. Immunostaining studies demonstrated the presence of intracellular immunoreactive ET, largely localized in perinuclear regions, which was greatly stimulated by TSH but not by TGF-beta. These observations suggest that TSH may stimulate only ET synthesis, whereas TGF-beta may stimulate both synthesis and secretion. Binding of [125I]ET-1 to receptor on thyroid cells was dose-dependently stimulated by TGF-beta (0-10 ng/ml) pretreatment for 3 days. Scatchard analysis of competitive binding data from TGF-beta (1 ng/ml)-treated cells indicated that increased binding was the result of increased receptor number and not increased receptor affinity. TSH (0-10 mU/ml), though not as potent as TGF-beta, also dose-dependently stimulated ET binding. Treatment of thyrocytes with 1 mU/ml TSH for 3 days did not significantly affect ET receptor number or binding affinity. These results illuminate aspects of a possible autocrine regulation of ET in the thyroid gland.

Adenoma↗
PubMed1993

Antibody-induced alterations of Na+/K(+)-ATPase activity in rabbit red blood cells during experimental thyroglobulin immunization.

Thyroid hormone modulates cell membrane Na+/K(+)-ATPase. A detailed study of erythrocyte membrane Na+/K(+)-ATPase activity was carried out during experimental thyroglobulin immunization. During the process of immunization there was a sharp decline in Na+/K(+)-ATPase activity until the 98th day of immunization, when the thyroglobulin antibody titer was at its peak. This enzyme activity retained a lower level although a fall in antibody titer occurred up to the 147th day.

Animals↗
PubMed1992

Dependence of carotid chemosensory responses on metabolic substrates.

The dependence of the carotid chemosensory response to hypoxia on metabolic substrate and the hypothesis that lactic acidosis is essential for O2 chemoreception were tested. Effects of 3 types of substrate (glucose, glutamate and a mixture of amino acids) on the response to hypoxia (perfusate flow interruption) were measured (n = 33 carotid bodies). The response to nicotine (n = 25) was used to determine whether these effects were exclusive to the hypoxic response. The cat carotid body was perfused and superfused in vitro with modified Tyrode solution (pO2 > 400 Torr, pCO2 < 1 Torr, pH = 7.4) at 36 degrees C containing a given substrate for at least 15 min prior to flow interruption or nicotine injection. Without substrate, responses to flow interruption (n = 4) and nicotine (n = 2) were irreversibly depressed. With glucose, responses to flow interruption (n = 13) and nicotine (n = 8) increased in a concentration-dependent fashion. Glutamate (42 mM) alone (n = 11) or a mixture of amino acids (4.2 mM) plus 5.5 mM glucose (n = 12) substituted for 11 mM glucose (n = 10). Thus, glutamate (42 mM), or a mixture of amino acids (4.2 mM) or a high concentration of glucose (11 mM) can support chemosensory responses to flow interruption and nicotine. Since glutamate undergoes oxidative deamination to alpha-ketoglutarate without lactic acid production, O2 chemoreception does not depend on lactic acidosis.

Amino Acids↗
PubMed1992

Control of metabolic and ventilatory responses to cold in anesthetized cats.

Interactions between the control of thermogenesis and ventilation were studied during normoxia, hyperoxia, and ambient or CO hypoxia in adult anesthetized intact or carotid-denervated cats. Shivering, metabolic and ventilatory responses to cold stress were studied. In addition, the effects of transient pharmacological stimulation (NaCN) or inhibition (Dopamine) of arterial chemoreceptor activity were studied under different levels of oxygenation. In intact animals, cold exposure provoked increases in VO2 and ventilation which were directly proportional to the intensity of shivering. During ambient or CO hypoxia, VO2 was less than in normoxia for all values of shivering intensity, suggesting that a non-shivering thermogenesis component may also be inhibited by hypoxia. The decrease in VO2 was associated with a smaller decrease in ventilation in ambient than in CO hypoxia because of the presence of the chemoreflex drive during ambient hypoxia. Pharmacological changes in chemoreceptor activity induced transient and opposite changes in ventilation and shivering intensity, confirming their role in the control of thermogenesis. After carotid denervation, when the drug effects were inconsistent or absent, changes in levels of oxygenation were still followed by changes in shivering activity and associated changes in VO2 and ventilation. We conclude that control of thermogenesis and ventilation and their interaction may be mediated by chemoreceptors as well as by direct effects upon central, possibly diencephalic structures.

Animals↗