Oxidative Stress Augments Chemoreflex Sensitivity in Rats Exposed to Chronic Intermittent Hypoxia

Overview

Journal Respir Physiol Neurobiol

Specialty Pulmonary Medicine

Date 2016 Sep 7

PMID 27595979

Citations 15

Authors

Barbara J Morgan

Melissa L Bates

Rodrigo Del Rio

Zunyi Wang

John M Dopp

Affiliations

Soon will be listed here.

Abstract

Chronic exposure to intermittent hypoxia (CIH) elicits plasticity of the carotid sinus and phrenic nerves via reactive oxygen species (ROS). To determine whether CIH-induced alterations in ventilation, metabolism, and heart rate are also dependent on ROS, we measured responses to acute hypoxia in conscious rats after 14 and 21 d of either CIH or normoxia (NORM), with or without concomitant administration of allopurinol (xanthine oxidase inhibitor), combined allopurinol plus losartan (angiotensin II type 1 receptor antagonist), or apocynin (NADPH oxidase inhibitor). Carotid body nitrotyrosine production was measured by immunohistochemistry. CIH produced an increase in the ventilatory response to acute hypoxia that was virtually eliminated by all three pharmacologic interventions. CIH caused a robust increase in carotid body nitrotyrosine production that was greatly attenuated by allopurinol plus losartan and by apocynin but unaffected by allopurinol. CIH caused a decrease in metabolic rate and a reduction in hypoxic bradycardia. Both of these effects were prevented by allopurinol, allopurinol plus losartan, and apocynin.

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References

Rotenberg B, Vicini C, Pang E, Pang K . Reconsidering first-line treatment for obstructive sleep apnea: a systematic review of the literature. J Otolaryngol Head Neck Surg. 2016; 45:23. PMC: 4822285. DOI: 10.1186/s40463-016-0136-4. View

Del Rio R, Moya E, Iturriaga R . Differential expression of pro-inflammatory cytokines, endothelin-1 and nitric oxide synthases in the rat carotid body exposed to intermittent hypoxia. Brain Res. 2011; 1395:74-85. DOI: 10.1016/j.brainres.2011.04.028. View

Schultz H, Marcus N, Del Rio R . Mechanisms of carotid body chemoreflex dysfunction during heart failure. Exp Physiol. 2014; 100(2):124-9. PMC: 4638138. DOI: 10.1113/expphysiol.2014.079517. View

Zimmerman M, Lazartigues E, Lang J, Sinnayah P, Ahmad I, Spitz D . Superoxide mediates the actions of angiotensin II in the central nervous system. Circ Res. 2002; 91(11):1038-45. DOI: 10.1161/01.res.0000043501.47934.fa. View

Carlson J, Hedner J, Sellgren J, Elam M, Wallin B . Depressed baroreflex sensitivity in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 1996; 154(5):1490-6. DOI: 10.1164/ajrccm.154.5.8912770. View

Cross K, Tizard J, TRYTHALL D . The gaseous metabolism of the newborn infant breathing 15% oxygen. Acta Paediatr (Stockh). 1958; 47(3):217-37. DOI: 10.1111/j.1651-2227.1958.tb07879.x. View

Sacramento J, Gonzalez C, Gonzalez-Martin M, Conde S . Adenosine Receptor Blockade by Caffeine Inhibits Carotid Sinus Nerve Chemosensory Activity in Chronic Intermittent Hypoxic Animals. Adv Exp Med Biol. 2015; 860:133-7. DOI: 10.1007/978-3-319-18440-1_15. View

Jelic S, Padeletti M, Kawut S, Higgins C, Canfield S, Onat D . Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation. 2008; 117(17):2270-8. PMC: 2844329. DOI: 10.1161/CIRCULATIONAHA.107.741512. View

Mifflin S, Cunningham J, Toney G . Neurogenic mechanisms underlying the rapid onset of sympathetic responses to intermittent hypoxia. J Appl Physiol (1985). 2015; 119(12):1441-8. PMC: 4683347. DOI: 10.1152/japplphysiol.00198.2015. View

10.

Pawar A, Nanduri J, Yuan G, Khan S, Wang N, Kumar G . Reactive oxygen species-dependent endothelin signaling is required for augmented hypoxic sensory response of the neonatal carotid body by intermittent hypoxia. Am J Physiol Regul Integr Comp Physiol. 2008; 296(3):R735-42. PMC: 2665844. DOI: 10.1152/ajpregu.90490.2008. View

11.

Lai C, Yang C, Hsu Y, Lin Y, Kuo T . Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats. J Appl Physiol (1985). 2006; 100(6):1974-82. DOI: 10.1152/japplphysiol.01051.2005. View

12.

Kumar G, Rai V, Sharma S, Ramakrishnan D, Peng Y, Souvannakitti D . Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress. J Physiol. 2006; 575(Pt 1):229-39. PMC: 1819426. DOI: 10.1113/jphysiol.2006.112524. View

13.

Marcus N, Philippi N, Bird C, Li Y, Schultz H, Morgan B . Effect of AT1 receptor blockade on intermittent hypoxia-induced endothelial dysfunction. Respir Physiol Neurobiol. 2012; 183(2):67-74. PMC: 3409315. DOI: 10.1016/j.resp.2012.05.025. View

14.

Dopp J, Philippi N, Marcus N, Olson E, Bird C, Moran J . Xanthine oxidase inhibition attenuates endothelial dysfunction caused by chronic intermittent hypoxia in rats. Respiration. 2011; 82(5):458-67. PMC: 3214835. DOI: 10.1159/000329341. View

15.

Fletcher E, Lesske J, BEHM R, Miller 3rd C, Stauss H, Unger T . Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea. J Appl Physiol (1985). 1992; 72(5):1978-84. DOI: 10.1152/jappl.1992.72.5.1978. View

16.

Olson Jr E . Physiological dead space increases during initial hours of chronic hypoxemia with or without hypocapnia. J Appl Physiol (1985). 1994; 77(3):1526-31. DOI: 10.1152/jappl.1994.77.3.1526. View

17.

Hashimoto Y, Itoh K, Nishida K, Okano T, Miyazawa Y, Okinaga K . Rapid superoxide production by endothelial cells and their injury upon reperfusion. J Surg Res. 1994; 57(6):693-7. DOI: 10.1006/jsre.1994.1203. View

18.

Peng Y, Yuan G, Ramakrishnan D, Sharma S, Bosch-Marce M, Kumar G . Heterozygous HIF-1alpha deficiency impairs carotid body-mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia. J Physiol. 2006; 577(Pt 2):705-16. PMC: 1890436. DOI: 10.1113/jphysiol.2006.114033. View

19.

Olea E, Agapito M, Gallego-Martin T, Rocher A, Gomez-Nino A, Obeso A . Intermittent hypoxia and diet-induced obesity: effects on oxidative status, sympathetic tone, plasma glucose and insulin levels, and arterial pressure. J Appl Physiol (1985). 2014; 117(7):706-19. DOI: 10.1152/japplphysiol.00454.2014. View

20.

Rymsa B, Wang J, De Groot H . O2-. release by activated Kupffer cells upon hypoxia-reoxygenation. Am J Physiol. 1991; 261(4 Pt 1):G602-7. DOI: 10.1152/ajpgi.1991.261.4.G602. View