Browsing by Author "Iturriaga, R"
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- ItemCardiovascular and ventilatory acclimatization induced by chronic intermittent hypoxia(2005) Iturriaga, R; Rey, S; Del Río, RPatients with obstructive sleep apnea (OSA) show augmentes ventilatory, sympathetic and cardiovascular responses to hypoxia. The facilitatory effect of chronic intermittent hypoxia (CIH) on the hypoxic ventilatory response has been attributed to a potentiation of the carotid body (CB) chemosensory response to hypoxia. However. it is a matter of debate whether the effects induced by CIH oil ventilatory responses to hypoxia are due to all enhanced CB activity. Recently, we studied the effects of short cyclic hypoxic episodes oil cat cardiorespiratory reflexes, heart rate variability, and CB chemosensory activity. Cats were exposed to cyclic hypoxic episodes repealed during 8 hours for 4 days. Our results showed that CIH selcectively enhanced ventilatory and carotid chemosensory responses to acute hypoxia. Exposure to CIH did not increase basal arterial pressure, heart-rate. or-the changes induced by acute hypoxia. However. the spectral analysis of heart rate variability of CIH cats showed a marked increase of the low/high frequency ratio and an increased variability in the low frequency band of heart rate variability, similar to what is observed ill OSA patients. Thus, it is likely that the enhanced CB reactivity to hypoxia may contribute to the augmented ventilatory response to hypoxia.
- ItemDopamine modulates carotid nerve responses induced by acetylcholine on the cat petrosal ganglion in vitro(1999) Alcayaga, J; Varas, R; Arroyo, J; Iturriaga, R; Zapata, PWe have recently reponed that application of acetylcholine (ACh) or nicotine to the petrosal ganglion-the sensory ganglion of the glossopharyngeal nerve-elicits a burst of discharges in the carotid nerve branch, innervating the carotid body and sinus, but not in the glossopharyngeal branch, innervating the tongue and pharynx, Thus, the perikarya of sensory neurons for the carotid bifurcation exhibit selective cholinosensitivity. Since dopamine (DA) modulates carotid nerve chemosensory activity, we searched for the presence of DA sensitivity at the perikarya of these neurons in the cat petrosal ganglion superfused in vitro. Applications of DA in doses of up to 5 mg to the ganglion did not modify the rate of spontaneous discharges in the carotid nerve, However, if DA was applied 30 s before ACh injections, ACh-evoked reactions were modified: low doses of DA enhanced the subsequent responses to ACh, while high doses of DA depressed the responses to ACh. This depressant effect of DA on ACh responses was partially antagonized by adding spiroperone to the superfusate. Our results show that the response to ACh of petrosal ganglion neurons projecting through the carotid nerve is modulated by DA acting on D-2 receptors located in the somata of these neurons. Thus, dopaminergic modulation of cholinosensitivity could be shared also by the membranes of peripheral endings and perikarya of primary sensory neurons involved in arterial chemoreception. (C) 1999 Elsevier Science B.V. All rights reserved.
- ItemEffects of CO2-HCO3- on catecholamine efflux from cat carotid body(1998) Iturriaga, R; Alcayaga, JUsing a chronoamperometric technique with carbon-fiber microelectrodes and neural recordings, we simultaneously measured the effects of the following procedures on catecholamine efflux (Delta CA) and frequency of chemosensory discharges (f(x)) from superfused cat carotid body: 1) the addition of CO2-HCO3- to Tyrode solution previously buffered with N-2-hydroxyethylpiperazine-N'-2-ethane-sulfonic acid, maintaining pH at 7.40; 2) hypercapnia (10% CO2, pH 7.10); 3) hypoxia (Po-2 h approximate to 40 Torr) with and without CO2-HCO3-; and 4) the impact of several boluses of dopamine (DA; 10-100 mu g) on hypoxic and hypercapnic challenges. With CO2-HCO3-, hypoxia increased f(x) which preceded Delta CA increases, whereas hypercapnia raised f(x) but did not consistently increase Delta CA. Repeated stimuli induced similar f(x) increases, but attenuated Delta CA. After DA, hypoxia produced larger Delta CA, which preceded chemosensory responses. Without CO2-HCO3-, hypoxia produced a similar pattern of Delta CA and f(x) responses. Switching to Tyrode solution with CO2-HCO3- at pH 7.40 raised f(x) but did not increase Delta CA. With CO2-HCO3- and after DA, hypoxic-induced Delta CAs were larger than in its absence. Results suggest that DA release is not essential for chemosensory excitation.
- ItemElectrophysiological characterization of nicotinic acetylcholine receptors in cat petrosal ganglion neurons in culture(2006) Varas, R; Valdés, V; Iturriaga-Vásquez, P; Cassels, BK; Iturriaga, R; Alcayaga, JPetrosal ganglion neurons are depolarized and fire action potentials in response to acetylcholine and nicotine. However, little is known about the subtype(s) of nicotinic acetylcholine receptors involved, although alpha 4 and alpha 7 subunits have been identified in petrosal ganglion neurons. Cytisine, an alkaloid unrelated to nicotine, and its bromo derivatives are agonists exhibiting different affinities, potencies and efficacies at nicotinic acetylcholine receptors containing a4 or 0 subunits. To characterize the receptors involved, we studied the effects of these agonists and the nicotinic acetylcholine receptor antagonists hexamethonium and alpha-bungarotoxin in isolated petrosal ganglion neurons. Petrosal ganglia were excised from anesthetized cats and cultured for up to 16 days. Using patch-clamp technique, we recorded whole-cell currents evoked by 5-10 s applications of acetylcholine, cytisine or its bromo derivatives. Agonists and antagonists were applied by gravity from a pipette near the neuron surface. Neurons responded to acetylcholine, cytisine, 3-bromocytisine and 5-bromocytisine with fast inward currents that desensitized during application of the stimuli and were reversibly blocked by 1 mu M hexamethoniurn or 10 nM alpha-bungarotoxin. The order of potency of the agonists was 3-bromocytisine >> acetylcholine congruent to cytisine >> 5-bromocytisine, suggesting that homomeric alpha 7 neuronal nicotinic receptors predominate in cat petrosal ganglion neurons in culture. (c) 2005 Elsevier B.V. All rights reserved.
- ItemInhibitory effects of NO on carotid body(2003) Valdés, V; Mosqueira, M; Rey, S; Del Rio, R; Iturriaga, RWe tested the hypothesis that nitric oxide (NO) produced within the carotid body is a tonic inhibitor of chemoreception and determined the contribution of neuronal and endothelial nitric oxide synthase (eNOS) isoforms to the inhibitory NO effect. Accordingly, we studied the effect of NO generated from S-nitroso-N-acetylpenicillamide (SNAP) and compared the effects of the nonselective inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) and the selective nNOS inhibitor 1-(2-trifluoromethylphenyl)- imidazole (TRIM) on chemosensory dose-response curves induced by nicotine and NaCN and responses to hypoxia (P-O2 approximate to 30 Torr). CBs excised from pentobarbitone-anesthetized cats were perfused in vitro with Tyrode at 38degreesC and pH 7.40, and chemosensory discharges were recorded from the carotid sinus nerve. SNAP (100 muM) reduced the responses to nicotine and NaCN. L-NAME (1 mM) enhanced the responses to nicotine and NaCN by increasing their duration, but TRIM (100 muM) only enhanced the responses to high doses of NaCN. The amplitude of the response to hypoxia was enhanced by L-NAME but not by TRIM. Our results suggest that both isoforms contribute to the NO action, but eNOS being the main source for NO in the cat CB and exerting a tonic effect upon chemoreceptor activity.
- ItemSodium nitroprusside blocks the cat carotid chemosensory inhibition induced by dopamine, but not that by hyperoxia(1998) Iturriaga, R; Alcayaga, J; Rey, SWe studied the effects of the nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), and the NO donor, sodium nitroprusside (SNP) on cat chemosensory responses to intravenous injections of NaCN (0.1-100 mu g/kg) and dopamine (0.1-20 mu g/kg), and to hyperoxic ventilation (100% O-2, 60-120 s). Cats were anesthetized with sodium pentobarbitone, paralyzed and artificially ventilated to prevent secondary ventilatory effects. The frequency of chemosensory discharges (f(x)) was recorded from one sectioned carotid sinus nerve. L-NAME (50 mg/kg i.v.) increased basal f(x) and slightly potentiated the responses to NaCN and dopamine. SNP (1-2 mg/kg i.v.) increased basal f(x), but reduced the NaCN-induced increases of f(x) over baseline and the transient f(x) inhibitions induced by dopamine, but not those produced by hyperoxia. Present results indicate that besides the known inhibitory effect of NO on chemosensory responses to low PO2, NO also blocks the chemosensory response to dopamine, leaving hyperoxic responses largely unchanged. (C) 1998 Elsevier Science B.V. All rights reserved.