Received September 12, 2006
Revised October 24, 2006
Accepted after revision November 15, 2006

¹ Case Western Reserve University

^* To whom correspondence should be addressed. E-mail: ted3{at}po.cwru.edu.

	Abstract

ABSTRACT The respiratory system expresses multiple forms of plasticity, defined as alterations in the breathing pattern that persist or develop after a stimulus. Stimulating breathing with intermittent hypoxia (IH) elicits long-term facilitation (LTF), a type of plasticity in which respiratory motor activity progressively increases in anesthetized animals, even after the stimuli have ceased and blood gases have normalized. It is unknown whether the sympathetic nervous system similarly expresses IH-induced plasticity, but we predicted that IH would evoke LTF in sympathetic nerve activity (SNA), because respiratory and sympathetic control systems are coupled. To test this idea, we recorded splanchnic (sSNA) and phrenic (PNA) nerve activities in equithesin-anesthetized rats. Animals were exposed to ten 45-s episodes of 8% O2/92% N2, separated by 5-min intervals of 100% O2, and recordings were continued for 60 min following the last hypoxic exposure. Cycle-triggered averages of integrated PNA and sSNA from periods preceding, and 5 and 60 min following the hypoxic stimuli were compared. Intermittent hypoxia significantly increased both sSNA and PNA. Treatment with methysergide (3 mg/kg, iv) 20 min prior to the intermittent hypoxic exposures prevented the increases in integrated PNA and sSNA 60-min after IH, indicating a role of serotinergic pathways in this form of plasticity. No increases in PNA and sSNA occurred at comparable times (60 & 120 min) in rats not exposed to hypoxia. The increased sSNA was not simply tonic, but was correlated with respiratory bursts, and occurred predominantly during the first half of expiration. These findings support the hypothesis that sympatho-respiratory coupling may underlie the sustained increase in SNA associated with the IH that occurs during sleep apnea.

Key Words: Hypoxia, Respiratory control, Sympathetic activity

This article has been cited by other articles:

				S. Rey, M. P. Tarvainen, P. A. Karjalainen, and R. Iturriaga Dynamic time-varying analysis of heart rate and blood pressure variability in cats exposed to short-term chronic intermittent hypoxia Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R28 - R37. [Abstract] [Full Text] [PDF]

				D. B. Zoccal, A. E. Simms, L. G. H. Bonagamba, V. A. Braga, A. E. Pickering, J. F. R. Paton, and B. H. Machado Increased sympathetic outflow in juvenile rats submitted to chronic intermittent hypoxia correlates with enhanced expiratory activity J. Physiol., July 1, 2008; 586(13): 3253 - 3265. [Abstract] [Full Text] [PDF]

				H. Wadhwa, C. Gradinaru, G. J. Gates, M. S. Badr, and J. H. Mateika Impact of intermittent hypoxia on long-term facilitation of minute ventilation and heart rate variability in men and women: do sex differences exist? J Appl Physiol, June 1, 2008; 104(6): 1625 - 1633. [Abstract] [Full Text] [PDF]

				J. A. Simpson, K. R. Brunt, and S. Iscoe Repeated inspiratory occlusions acutely impair myocardial function in rats J. Physiol., May 1, 2008; 586(9): 2345 - 2355. [Abstract] [Full Text] [PDF]

				Y.-H. Hsieh, T. E. Dick, and R. E. Siegel Adaptation to hypobaric hypoxia involves GABAA receptors in the pons Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R549 - R557. [Abstract] [Full Text] [PDF]

				H. D. Schultz, Y. L. Li, and Y. Ding Arterial Chemoreceptors and Sympathetic Nerve Activity: Implications for Hypertension and Heart Failure Hypertension, July 1, 2007; 50(1): 6 - 13. [Full Text] [PDF]