The underlying premise is that respiration can only be understood in the context of the interplay among controlled elements, the controller, and the nonrespiratory influences on both the controller and the controlled element, seen as an integrated system. Each element of the system contributes to the modulation of ventilation in the normal resting state, but the relative importance of these components may change under conditions of environmental stress or disease. This program consist of seven projects. Project 1 deals with the central factors that coordinate respiratory skeletal muscle function (Project 1A) and the medullary mechanisms concerned with integration and coordination of respiratory and cardiovascular responses (Project 1B). Project 2 evaluates the behavioral aspects of respiratory control and the relationship between the conscious perceptions of respiratory sensation to dyspnea and respiratory motor responses. Project 3 assesses the neuromuscular regulation of breathing in infants with emphasis on the function of upper airway muscles. Project 4 investigates breathing during sleep in adults. The focus of Project 4A is the functional responses of the upper airway muscles and their interrelationship with the geometry and dynamic mechanical properties of the upper airway; while Project 4B studies the mechanisms that produce and terminate recurrent apneas and periodic breathing. The emphasis of Project 5 is on the regulation of respiratory muscle blood flow and its role in adaptation to stress. Project 6 deals with the neural control of the respiratory muscles and how it is related to the cellular mechanisms that affect airway responses. The central regulation of airway smooth muscle activity is the focus of Project 6A; thermal factors acting reflexly and directly on the airway are studied in Project 6B; while Project 6C examines the effect of the intrinsic cellular characteristics of smooth muscle on airway responsivity. Project 7 explores the mechanisms which control the reactions of the lung to injury and their possible implications in the control of breathing. Basic data will be obtained on the organization and operation of the respiratory controller and its interaction with other control systems. Additionally, the studies have been designed to identify mechanisms and risk factors at the system and cellular level for respiratory failure which will be useful in devising and evaluating therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL025830-10
Application #
3097912
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1981-04-01
Project End
1991-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Prabhakar, Nanduri R; Semenza, Gregg L (2012) Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. Physiol Rev 92:967-1003
Kline, David D (2010) Chronic intermittent hypoxia affects integration of sensory input by neurons in the nucleus tractus solitarii. Respir Physiol Neurobiol 174:29-36
Peng, Y-J; Nanduri, J; Yuan, G et al. (2009) NADPH oxidase is required for the sensory plasticity of the carotid body by chronic intermittent hypoxia. J Neurosci 29:4903-10
Kline, David D; Hendricks, Gabriel; Hermann, Gerlinda et al. (2009) Dopamine inhibits N-type channels in visceral afferents to reduce synaptic transmitter release under normoxic and chronic intermittent hypoxic conditions. J Neurophysiol 101:2270-8
Prabhakar, Nanduri R; Kumar, Ganesh K; Nanduri, Jayasri (2009) Intermittent hypoxia-mediated plasticity of acute O2 sensing requires altered red-ox regulation by HIF-1 and HIF-2. Ann N Y Acad Sci 1177:162-8
Braga, Valdir A; Prabhakar, Nanduri R (2009) Refinement of telemetry for measuring blood pressure in conscious rats. J Am Assoc Lab Anim Sci 48:268-71
Kline, David D (2008) Plasticity in glutamatergic NTS neurotransmission. Respir Physiol Neurobiol 164:105-11
Buniel, Maria; Glazebrook, Patricia A; Ramirez-Navarro, Angelina et al. (2008) Distribution of voltage-gated potassium and hyperpolarization-activated channels in sensory afferent fibers in the rat carotid body. J Comp Neurol 510:367-77
Pawar, Anita; Peng, Ying-Jie; Jacono, Frank J et al. (2008) Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia. J Appl Physiol 104:1287-94
Hsieh, Yee-Hsee; Dick, Thomas E; Siegel, Ruth E (2008) Adaptation to hypobaric hypoxia involves GABA A receptors in the pons. Am J Physiol Regul Integr Comp Physiol 294:R549-57

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