The proposal deals with the interrelationship between peripheral chemosensory mechanisms and the activity of the sympathetic nervous system. The specific objectives are to understand how and to what extent the activities of the pre- and postganglionic fibers to the superior cervical ganglion are regulated by the activties of the peripheral chemoreceptors, respiratory drives from the central nervous system, by the local effects of PO2 and PCO2 on the sympathetic ganglia and by the endogenous dopaminergic mechanisms. The proposal grew out of our active interest in the peripheral chemoreceptors and respiratory chemoreflexes and of the consideration that the existing knowledge in the area does not answer the quantitative as well as qualitative questions raised. The specific experimental procedure is to quantitate pre- and postganglionic nerve responses to selective experimental interventions in anesthetized or unanesthetized decerebrated and spinalized (at C-1 level) cats. One kind of intervention deals with the reflex response of the cervical sympathetic nerves to the chemosensory input in the presence and absence of rhythmic respiratory discharge. The second series deals with the definition of chemosensory properties of the peripheral sympathetic neurons and ganglia independent of the peripheral chemoreceptors and respiratory drive. The third series examines the hypothesis that the endogenous dopaminergic system plays a critical role in the regulation of the postganglionic nerve activity. Perfused superior cervical ganglia will be used to conduct a part of the study. The proposed experimental study is important because the results (1) will tell us how the sympathetic nerve activity is reflexly regulated by the stimuli related to respiration; (2) will extend the observations on the inherent chemosensory properties of the peripheral sympathetic ganglia and compare with those of carotid and aortic bodies; and (3) will indicate the role of the peripheral dopaminergic system in the responses of the sympathetic ganglia. These results will provide the basis for further study of the cellular mechanisms of chemosensing common to both peripheral chemoreceptors and sympathetic ganglia. The practical health related implications are that the chemosensory and chemoreflex control of sympathetic (and reciprocally parasympathetic) nerve activities is critically relevant to respiratory airway and vascular diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021068-04
Application #
3401852
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1984-12-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Di Giulio, C; Huang, W X; Mokashi, A et al. (2003) Sustained hypoxia promotes hyperactive response of carotid body in the cat. Respir Physiol Neurobiol 134:69-74
Di Giulio, C; Data, P G; Lahiri, S (1991) Chronic cobalt causes hypertrophy of glomus cells in the rat carotid body. Am J Physiol 261:C102-5
Lahiri, S; Huang, W X; Mokashi, A (1991) Carotid chemosensory timing effects on cervical sympathetic discharges in the cat. J Auton Nerv Syst 33:65-78
Lahiri, S; Mokashi, A; Shirahata, M et al. (1990) Chemical respiratory control in chronically hyperoxic cats. Respir Physiol 82:201-15
Di Giulio, C; Huang, W X; Lahiri, S et al. (1990) Cobalt stimulates carotid body chemoreceptors. J Appl Physiol 68:1844-9
Lahiri, S; Mokashi, A; Huang, W et al. (1989) Stimulus interaction between CO2 and almitrine in the cat carotid chemoreceptors. J Appl Physiol 67:232-8
Santolaya, R B; Lahiri, S; Alfaro, R T et al. (1989) Respiratory adaptation in the highest inhabitants and highest Sherpa mountaineers. Respir Physiol 77:253-62
Huang, W X; Lahiri, S; Mokashi, A et al. (1989) Sympathetic peripheral chemoreflex is independent of expiratory output neurons in the cat. J Auton Nerv Syst 29:29-39
Hsiao, C; Lahiri, S; Mokashi, A (1989) Peripheral and central dopamine receptors in respiratory control. Respir Physiol 76:327-36
Huang, W; Lahiri, S; Mokashi, A et al. (1988) Relationship between sympathetic and phrenic nerve responses to peripheral chemoreflex in the cat. J Auton Nerv Syst 25:95-105

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