Effect of endothelin antagonism on apnea frequency following chronic intermittent hypoxia.
Chronic hypoxia increases the hypoxic ventilatory response (HVR). Augmented HVR contributes to central apneas seen in heart failure and complex sleep apnea. Endothelin receptor (ETR) antagonism decreases carotid body afferent activity following chronic intermittent hypoxia (CIH). We speculated ETR antagonism would reduce HVR and apneas following CIH. HVR and apneas were measured after exposure to CIH and room air sham (SHAM). ETR blocker Ambrisentan was administered via the chow of CIH-exposed animals from days 1 to 12 of CIH (CIH/AMB). A separate crossover group was exposed to CIH and fed normal chow (placebo) days 1-6, and Ambrisentan days 7-12 (CIH/PLA-AMB). SHAM and CIH/PLA animals were fed placebo days 1-12. The CIH/AMB and CIH/PLA-AMB rats had reduced HVR compared to CIH/PLA, similar HVR compared to sham exposed animals, and reduced apnea frequency compared to CIH/PLA animals. The reduced HVR and post-hypoxic apneas resulting from Ambrisentan administration suggests ETR antagonists may have utility in reducing central apneas following CIH.
Beth Israel Deaconess Medical Center, Division of Pulmonary Critical Care, and Sleep Medicine, Boston, MA, United States. Electronic address: ldonovan@bidmc.harvard.edu.
Lucas M
LM
Donovan
Beth Israel Deaconess Medical Center, Division of Pulmonary Critical Care, and Sleep Medicine, Boston, MA, United States.
Yuzhen
Y
Liu
Beth Israel Deaconess Medical Center, Division of Pulmonary Critical Care, and Sleep Medicine, Boston, MA, United States.
J Woodrow
JW
Weiss
D000818:Animals; D001049:Apnea / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D002908:Chronic Disease; D018592:Cross-Over Studies; D065130:Endothelin A Receptor Antagonists; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D019141:Respiratory System Agents / Q000494:pharmacology*; D012146:Rest
D065130:Endothelin A Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; D044022:Receptor, Endothelin A; D019141:Respiratory System Agents; C467894:ambrisentan
Apnea; Control of breathing; Endothelin; Hypoxic response