H2S mediates carotid body response to hypoxia but not anoxia.

Abstract

The role of cystathionine-γ-lyase (CSE) derived H2S in the hypoxic and anoxic responses of the carotid body (CB) were examined. Experiments were performed on Sprague-Dawley rats, wild type and CSE knockout mice on C57BL/6 J background. Hypoxia (pO2 = 37 ± 3 mmHg) increased the CB sensory nerve activity and elevated H2S levels in rats. In contrast, anoxia (pO2 = 5 ± 4 mmHg) produced only a modest CB sensory excitation with no change in H2S levels. DL-propargylglycine (DL-PAG), a blocker of CSE, inhibited hypoxia but not anoxia-evoked CB sensory excitation and [Ca2+]i elevation of glomus cells. The inhibitory effects of DL-PAG on hypoxia were seen: a) when it is dissolved in saline but not in dimethyl sulfoxide (DMSO), and b) in glomus cells cultured for18 h but not in cells either soon after isolation or after prolonged culturing (72 h) requiring 1-3 h of incubation. On the other hand, anoxia-induced [Ca2+]i responses of glomus cell were blocked by high concentration of DL-PAG (300μM) either alone or in combination with aminooxyacetic acid (AOAA; 300μM) with a decreased cell viability. Anoxia produced a weak CB sensory excitation and robust [Ca2+]i elevation in glomus cells of both wild-type and CSE null mice. As compared to wild-type, CSE null mice exhibited impaired CB chemo reflex as evidenced by attenuated efferent phrenic nerve responses to brief hyperoxia (Dejours test), and hypoxia. Inhalation of 100% N2 (anoxia) depressed breathing in both CSE null and wild-type mice. These observations demonstrate that a) hypoxia and anoxia are not analogous stimuli for studying CB physiology and b) CSE-derived H2S contributes to CB response to hypoxia but not to that of anoxia.

• Authors: Ying-Jie Peng, Vladislav V Makarenko, Anna Gridina, Irina Chupikova, Xiuli Zhang, Ganesh K Kumar, Aaron P Fox, Nanduri R Prabhakar
• Journal: Respiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 259 Pg. 75-85 (01 2019) ISSN: 1878-1519 [Electronic] Netherlands
• PMID: 30086385 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Sulfites
• Cystathionine gamma-Lyase
• hydrogen sulfite
• Calcium

Topics

• Action Potentials (drug effects)
• Animals
• Calcium (metabolism)
• Carotid Body (drug effects, pathology)
• Cells, Cultured
• Cystathionine gamma-Lyase (genetics, metabolism)
• Hypoxia (drug therapy, pathology)
• Male
• Phrenic Nerve (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Sulfites (pharmacology, therapeutic use)