Published Online
on November 3, 2003

A more recent version of this article appeared on December 1, 2003

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Submitted on July 22, 2003
Revised on August 13, 2003

Regulation of Catecholamines by Sustained and Intermittent Hypoxia in Neuroendocrine Cells and Sympathetic Neurons

Anna S. Hui; Justin B. Striet; Gary Gudelsky; Galia K. Soukhova; Evelyne Gozal; Dana Beitner-Johnson; Shang-Z. Guo; Leroy R. Sachleben Jr; John W. Haycock; David Gozal; and Maria F. Czyzyk-Krzeska^*

From the Departments of Genome Science (A.S.H., J.B.S., D.B.-J., M.F.C.-K.), and Molecular and Cellular Physiology (D.B.-J., M.F.C.-K.), College of Medicine, College of Pharmacy (G.G.), University of Cincinnati, Cincinnati, Ohio; Kosair Children’s Hospital Research Institute and Departments of Pediatrics, Pharmacology, and Toxicology (G.K.S., E.G., S.Z.-G., L.R.S., D.G.), University of Louisville, Louisville, Ky; and the Department of Biochemistry and Molecular Biology (J.W.H.), Louisiana State University Health Sciences Center, New Orleans, La.

^* To whom correspondence should be addressed. E-mail: Maria.Czyzykkrzeska{at}uc.edu.

Abstract--Chronic intermittent hypoxia, a characteristic feature of sleep-disordered breathing, induces hypertension through augmented sympathetic nerve activity and requires the presence of functional carotid body arterial chemoreceptors. In contrast, chronic sustained hypoxia does not alter blood pressure. We therefore analyzed the biosynthetic pathways of catecholamines in peripheral nervous system structures involved in the pathogenesis of intermittent hypoxia-induced hypertension, namely, carotid bodies, superior cervical ganglia, and adrenal glands. Rats were exposed to either intermittent hypoxia (90 seconds of room air alternating with 90 seconds of 10% O₂) or to sustained hypoxia (10% O₂) for 1 to 30 days. Dopamine, norepinephrine, epinephrine, dihydroxyphenylacetic acid, and 5-hydroxytyptamine contents were measured by high-performance liquid chromatography. Expression of tyrosine hydroxylase and its phosphorylated forms, dopamine -hydroxylase, phenylethanolamine N-methyltransferase, and GTP cyclohydrolase-1 were determined by Western blot analyses. Both sustained and intermittent hypoxia significantly increased dopamine and norepinephrine content in carotid bodies but not in sympathetic ganglia or adrenal glands. In carotid bodies, both types of hypoxia augmented total levels of tyrosine hydroxylase protein and its phosphorylation on serines 19, 31, 40, as well as levels of GTP cyclohydrolase-1. However, the effects of intermittent hypoxia on catecholaminergic pathways were significantly smaller and delayed than those induced by sustained hypoxia. Thus, attenuated induction of catecholaminergic phenotype by intermittent hypoxia in carotid body may play a role in development of hypertension associated with sleep-disordered breathing. The effects of both types of hypoxia on expression of catecholaminergic enzymes in superior cervical neurons and adrenal glands were transient and small.

Key words: blood pressure • catecholamines • chemoreceptors • sympathetic nervous system • sleep apnea syndromes • oxygen • adrenal gland

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