Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii - a microinjection study in the rat.
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1. The effect of microinjecting angiotensin II (ANGII) into the nucleus of the solitary tract (NTS) on both baroreceptor and peripheral chemoreceptor reflexes was compared. 2. Experiments were performed in a working heart-brainstem preparation of rat. Baroreceptors were stimulated by raising perfusion pressure and chemoreceptors were activated with aortic injections of sodium cyanide (0.025 %, 25-75 microl). Reflex changes in phrenic nerve activity and heart rate were measured after bilateral NTS microinjection (50 nl) of ANGII (0.5-5000 fmol). 3. NTS microinjection of 5 fmol ANGII elicited a transient (28.2 +/- 6 s; mean +/- s.e.m.) bradycardia (-18 +/- 3 beats min-1), and decreased phrenic nerve activity cycle length and amplitude (P < 0.05). At higher doses of ANGII a similar respiratory response was seen but heart rate changes were inconsistent. 4. The baroreceptor reflex bradycardia was depressed significantly by NTS microinjections of ANGII (5-5000 fmol) in a dose-dependent manner with the reflex gain decreasing from 1.7 +/- 0.16 to 0.66 +/- 0.1 beats min-1 mmHg-1 (P < 0.01) at 5000 fmol. Although the chemoreceptor reflex bradycardia was depressed at a low dose of ANGII (5 fmol), all higher doses (50-5000 fmol) produced a dose-dependent potentiation of the reflex bradycardia (maximally +64 +/- 8 %). The respiratory component was unaffected. The effects of ANGII on both reflexes were blocked by an ANGII type 1 (AT1) receptor antagonist, losartan (20 microM). 5. The potentiating action of ANGII on the chemoreceptor reflex cardiac response was abolished by a neurokinin type 1 (NK1) receptor blocker (CP-99,994, 5 microM) but this had no effect on the baroreceptor reflex. 6. AT1 receptors in the NTS can depress the baroreceptor reflex bradycardia which is independent of NK1 receptors. The ANGII effect on the cardiac component of the chemoreceptor reflex is bi-directional being inhibited at low concentrations and potentiated at higher concentrations; the latter involves NK1 receptors and presumably results from release of substance P. (+info)
Differential effects of angiotensin II in the nucleus tractus solitarii of the rat--plausible neuronal mechanism.
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1. Cellular mechanisms of the actions of angiotensin II (ANGII) within the nucleus of the solitary tract (NTS) were studied using rat brain slices in 78 neurones recorded in the whole-cell configuration. Twenty-nine per cent of cells had an on-going activity and with only one exception these cells responded to tractus solitarii (TS) stimulation with a monophasic excitatory postsynaptic potential (EPSP). In approximately half of the silent cells, TS stimulation evoked an EPSP-inhibitory postsynaptic potential (IPSP) complex. 2. The ANGII (200 or 1000 nM) effect on TS-evoked EPSPs depended on the cell subpopulation. In cells with on-going activity, ANGII (1000 nM) increased evoked EPSP amplitude by +70 +/- 13 % (means +/- s.e.m., n = 5) but reduced it (200 and 1000 nM) in silent cells where both evoked EPSPs and IPSPs were present. ANGII either increased TS-evoked IPSP conductances in cells where they were detectable or revealed an evoked IPSP (200 nM ANGII: IPSP conductance increased from 70 +/- 29 to 241 +/- 34 pS; n = 11). All ANGII effects were prevented by the ANGII type 1 (AT1) receptor blocker losartan. Since 200 nM ANGII did not increase responses to iontophoretically applied GABA, the effect of ANGII on TS-evoked IPSPs may occur presynaptically. 3. The neurokinin type 1 (NK1) receptor antagonist CP-99,994 (5 microM) blocked the ANGII-induced increase in EPSPs but had no effect on TS-evoked IPSP potentiation by ANGII. 4. Thus, ANGII can potentiate both inhibitory and excitatory synaptic transmission within different subpopulations of NTS neurones. Potentiation of evoked EPSPs, but not of IPSPs, involves activation of NK1 receptors. The balance of these actions of ANGII could be reflex specific: for the baroreflex circuitry the inhibitory action might predominate while the peripheral chemoreceptor reflex may be facilitated due to enhanced excitatory transmission. (+info)
Identification of fast and slow ventilatory responses to carbon dioxide under hypoxic and hyperoxic conditions in humans.
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1. Under conditions of both euoxia and hypoxia, it is generally accepted that the ventilatory response to CO2 has both rapid (peripheral chemoreflex) and slow (central chemoreflex) components. However, under conditions of hyperoxia, it is unclear in humans whether the fast component is completely abolished or merely attenuated in magnitude. 2. The present study develops a technique to determine whether or not a two-compartment model fits the ventilatory response to CO2 significantly better than a one-compartment model. Data were collected under both hypoxic (end-tidal PO2 = 50 Torr) conditions, when two components would be expected, and under hyperoxic (end-tidal PO2 = 200 Torr) conditions, when the presence of the fast compartment is under question. 3. Ten subjects were recruited, of whom nine completed the study. The end-tidal PCO2 of each subject was varied according to a multi-frequency binary sequence that involved 13 steps into and 13 steps out of hypercapnia lasting altogether 1408 s. 4. In four out of nine subjects in hypoxia, and six out of nine subjects in hyperoxia, the two-compartment model fitted the data significantly better than the one-compartment model (F ratio test on residuals). This improvement in fit was significant for the pooled data in both hypoxia (P < 0.05) and hyperoxia (P < 0.005). Mean ventilatory sensitivities for the central chemoreflex were (mean +/- s.e.m.) 1. 69 +/- 0.39 l min-1 Torr-1 in hypoxia and 2.00 +/- 0.32 l min-1 Torr-1 in hyperoxia. Mean ventilatory sensitivities for the peripheral chemoreflex were 2.42 +/- 0.36 l min-1 Torr-1 in hypoxia and 0.75 +/- 0.16 l min-1 Torr-1 in hyperoxia. 5. It is concluded that the rapid and slow components of the ventilatory response to CO2 can be separately identified, and that a rapid component persists under conditions of hyperoxia. (+info)
Effects of somatostatin on the control of breathing in humans.
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1. Somatostatin depresses the ventilatory response to hypoxia (AHVR). This study sought to determine whether somatostatin also reduced the peripheral chemoreflex sensitivity to hypercapnia, and if so, whether this was related to the reduction in AHVR. 2. Nine subjects completed the study. AHVR and the ventilatory responses to hypercapnia under both hyperoxic and hypoxic conditions were assessed both without and with an infusion of somatostatin (0.5 BsBs5mgBs5 h-1). Peripheral (fast) and central (slow) responses to hypercapnia were distingushed by use of a multi-frequency binary sequence input in end-tidal PCO2 (PET,CO2) that included 13 steps into and out of hypercapnia. 3. The acute ventilatory response to a reduction in end-tidal PO2 (PET,O2) from 100 to 50 Torr (at a PET, CO2 of +1.5-2.0 Torr above normal) was reduced from (mean +/- s.e.m. ) 16.4 +/- 3.3 to 9.5 +/- 3.2 l min-1 (P < 0.005, Student's t test) by somatostatin. The magnitude of the ensuing hypoxic ventilatory decline was unaltered (8.8 +/- 2.7 l min-1 in control vs. 8.0 +/- 2. 9 l min-1 with somatostatin). 4. The peripheral chemoreflex sensitivity to CO2 in hypoxia was reduced from 2.42 +/- 0.36 to 1.18 +/- 0.20 l min-1 Torr-1 (P < 0.005) with somatostatin. The reduction under hyperoxic conditions from 0.75 +/- 0.34 to 0.49 +/- 0.09 l min-1 Torr-1 did not reach significance. Central chemoreflex sensitivity to CO2 was unchanged. Changes in peripheral chemoreflex sensitivity to CO2 in hypoxia correlated with changes in AHVR. 5. We conclude that peripheral chemoreflex sensitivity to CO2 is reduced by somatostatin, probably via the same mechanism as that by which somatostatin exerts its effects on AHVR. (+info)
Olfactory receptor database: a sensory chemoreceptor resource.
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The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemo-receptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has been constructed and is publicly available in a pilot mode. The database schema of ORDB has been changed from traditional relational to EAV/CR (Entity-Attribute-Value with Classes and Relationships), which allows the interoperability of ORDB with other related databases as well as the creation of intra-database associations among objects. This inter-operability facilitates users to follow information from odor molecule binding to its putative receptor, to the properties of the neuron expressing the receptor, to a computational model of activity of olfactory bulb neurons. In addition, tools and resources have been added allowing users to access interactive phylogenetic trees and alignments of sensory chemoreceptors. ORDB is available via the WWW at http://ycmi.med. yale.edu/senselab/ordb/ (+info)
Contribution of carotid chemoreceptors to mesenteric venoconstriction during acute hypercapnia in rabbits.
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The contribution of carotid chemoreceptors to hypercapnia-induced mesenteric venoconstriction was examined in 12 alpha-chloralose-anesthetized rabbits (1.0-1.6 kg). Surgical preparation consisted of a tracheotomy, femoral arterial and venous cannulation, and a midline laparotomy through which a 13-cm loop of ileum was exteriorized and superfused with physiological salt solution. Mesenteric vein diameter and intravenous pressure (using a servo-null measurement system) were measured in 500- to 1,000-micron mesenteric veins during 40-s periods of 15%, 20%, and 25% CO2 inhalation. Measurements were then repeated following bilateral ablation of the carotid chemoreceptors. Before denervation, mesenteric vein diameter constricted 6.5 +/- 1.1%, 11.9 +/- 1.1%, and 17.9 +/- 2.2% during the 15%, 20%, and 25% CO2 inhalation, respectively. After denervation, these values were reduced to 5.0 +/- 0.9%, 6.9 +/- 1.2%, and 8.4 +/- 1.3%, respectively. We conclude that activation of the carotid chemoreceptors by hypercapnia induces active mesenteric venoconstriction. After denervation of the carotid baroreceptors and chemoreceptors, there was also a small decrease in venule diameter proportional to the level of inspired CO2. We further conclude that noncarotid body chemoreceptor activation contributes to mesenteric venular constriction. (+info)
Central nervous system regulation of reflex responses to hypotension during fetal life.
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The ability of the fetus to survive, grow, and successfully complete the transition from fetal to neonatal life is critically dependent on the appropriate regulation of fetal blood pressure, blood volume, and fluid dynamics. This is a short review of the physiological mechanisms controlling the fetal cardiovascular system, focusing mainly on the neural and endocrine elements in the schema of cardiovascular function and control. The fetal cardiovascular system is arranged anatomically to provide for perfusion of the umbilical-placental circulation, the organ of gas exchange of the fetus, and to largely bypass the lungs. Fetal blood volume and pressure, maintained at levels that are appropriate for this function, are influenced by neural and endocrine control mechanisms, which are similar to, but quantitatively different from, the adult animal. Baroreceptors and chemoreceptors located in the carotid sinuses and aortic arch sense changes in blood pressure and blood gases and comprise the afferent limb of the major reflexes that maintain normal fetal blood pressure and volume. Fetal hypotension stimulates reflex decreases in fetal heart rate, which are apparently mediated by chemoreceptor input. Arginine vasopressin responses to hypotension are most likely mediated by baroreceptor input. Recent evidence suggests that the reflex responses to hypotension in the fetus are modulated by paracrine or endocrine factors. For example, baroreceptor or chemoreceptor reflex pathways are modulated by the endogenous production of prostanoids and by the preparturient changes in fetal plasma estrogen concentration. (+info)
Chemoreceptors and feeding in calanoid copepods (Arthropoda: Crustacea).
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Ultrastructural studies of the mouthparts of the calanoid copepod Diaptomus pallidus have revealed the presence of numerous chemoreceptors, and the apparent absence of mechanoreceptors. The setae contain no muscles, and the setules are noncellular extensions of their chitin wall. This allows a new insight into the selective feeding of zooplankters. (+info)