Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There has been suggestion of a possible relationship between the intake of the appetite suppressant dexfenfluramine and the development of primary pulmonary hypertension. We investigated the pulmonary vascular effects of acute intravenous dexfenfluramine in pentobarbital-anesthetized dogs ventilated in hyperoxia (fraction of inspired oxygen, FIO2, 0.4) and either challenged with a FIO2 of 0.1 to induce hypoxic pulmonary hypertension (n = 20) or given autologous blood clots to induce embolic pulmonary hypertension (n = 6). Pulmonary vascular tone was evaluated by multipoint (mean pulmonary artery pressure [Ppa] - pulmonary artery occluded pressure [Ppao])/cardiac output (Q) plots. Hypoxia increased Ppa - Ppao over the entire range of Q studied, from 1.5 to 4.0 L/min/m2, in 12 dogs (responders) and had no significant effect on (Ppa - Ppao)/Q plots in 8 other dogs (nonresponders). Dexfenfluramine did not affect (Ppa - Ppao)/Q plots in 6 responders but shifted (Ppa - Ppao)/Q plots to higher pressures in hypoxia in 6 nonresponders (p < 0.001). Dexfenfluramine had no effect on (Ppa - Ppao)/Q plots in the 6 dogs with embolic pulmonary hypertension. Because dexfenfluramine has serotoninergic properties, we compared the effects of ketanserin, a serotonin (5-hydroxytryptamine, 5-HT) S2 receptor antagonist, on naturally present versus dexfenfluramine-restored hypoxic pulmonary vasoconstriction. Ketanserin did not affect hyperoxic or hypoxic pulmonary vascular tone, neither in 6 responders nor in 2 nonresponders with dexfenfluramine-restored hypoxic vasoconstriction. We conclude that dexfenfluramine restores hypoxic pulmonary vasoconstriction in dogs with weak or absent hypoxic pressor response and that this effect is unlikely to be mediated by activation of 5-HT S2 receptors.
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PMID:Effects of dexfenfluramine on hypoxic pulmonary vasoconstriction and embolic pulmonary hypertension in dogs. 788 58

We hypothesized that the 5-hydroxytryptamine (5-HT) active drugs ketanserin and 5-carboxamidotryptamine (5-CT) would modulate time-dependent hypoxic phrenic and hypoglossal responses, including 1) short-term hypoxic response, 2) posthypoxia frequency decline (PHFD), and 3) long-term facilitation (LTF) of respiratory motor output. Phrenic and hypoglossal nerve activities were recorded in urethan-anesthetized, paralyzed, vagotomized, and artificially ventilated rats pretreated either with ketanserin (5-HT(2A/C) antagonist; 2 mg/kg iv), 5-CT (5-HT(1A/B) agonist; 10 microg/kg iv), or saline (sham). Rats were exposed to three 5-min episodes of hypoxia [fractional inspired O(2) (FI(O2)) = 0.11], separated by 5 min of hyperoxia (FI(O2) = 0.5). During hypoxia, ketanserin augmented phrenic but not hypoglossal burst amplitude; 5-CT had no effect. Both drugs accentuated PHFD. Ketanserin blocked phrenic LTF; hypoglossal LTF was not apparent, even in sham-treated rats. 5-CT reversed LTF, resulting in a long-lasting depression of phrenic burst frequency and amplitude without effect on hypoglossal burst amplitude. The data suggest that 1) 5-HT(2A/C) receptor activation modulates the short-term hypoxic phrenic response and PHFD and is necessary for LTF; and 2) 5-CT may affect time-dependent hypoxic ventilatory responses by reducing serotonin release via 5-HT(1A/B) autoreceptor activation.
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PMID:Time-dependent hypoxic ventilatory responses in rats: effects of ketanserin and 5-carboxamidotryptamine. 1048 81

Inspiratory hypoglossal motoneurons (IHMNs) maintain upper airway patency. However, this may be compromised during sleep and by sedatives, potent analgesics, and volatile anesthetics by either depression of excitatory or enhancement of inhibitory inputs. In vitro data suggest that serotonin (5-HT), through the 5-HT2A receptor subtype, plays a key role in controlling the excitability of IHMNs. We hypothesized that in vivo 5-HT modulates IHMNs activity through the 5-HT2A receptor subtype. To test this hypothesis, we used multibarrel micropipettes for extracellular single neuron recording and pressure picoejection of 5-HT or ketanserin, a selective 5-HT2A receptor subtype antagonist, onto single IHMNs in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs. Drug-induced changes in neuronal discharge frequency (F(n)) and neuronal discharge pattern were analyzed using cycle-triggered histograms. 5-HT increased the control peak F(n) to 256% and the time-averaged F(n) to 340%. 5-HT increased the gain of the discharge pattern by 61% and the offset by 34 Hz. Ketanserin reduced the control peak F(n) by 68%, the time-averaged F(n) by 80%, and the gain by 63%. These results confirm our hypothesis that in vivo 5-HT is a potent modulator of IHMN activity through the 5-HT2A receptor subtype. Application of exogenous 5-HT shows that this mechanism is not saturated during hypercapnic hyperoxia. The two different mechanisms, gain modulation and offset change, indicate that 5-HT affects the excitability as well as the excitation of IHMNs in vivo.
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PMID:Serotonergic modulation of inspiratory hypoglossal motoneurons in decerebrate dogs. 1649 64