2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004100830v1 16/7/2081    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Klein, K. Articles by Schaefer, F. Search for Related Content PubMed PubMed Citation Articles by Klein, K. Articles by Schaefer, F.

Impaired Autofeedback Regulation of Hypothalamic Norepinephrine Release in Experimental Uremia

Katrin Klein^*, Markus Daschner^*, Marcel Vogel^*, Jun Oh^*, Thomas J. Feuerstein and Franz Schaefer^*

^* Division of Pediatric Nephrology, University Children’s Hospital, University of Heidelberg, Heidelberg, and Section of Clinical Neuropharmacology, University Hospital of Freiburg, Freiburg, Germany

Address correspondence to: Dr. Franz Schaefer, University Children’s Hospital, Im Neuenheimer Feld 150, Heidelberg 69120, Germany. Phone: +49-6221-563-2396; Fax: +49-6221-56-4203; E-mail: franz_schaefer{at}med.uni-heidelberg.de

Received for publication October 8, 2004. Accepted for publication March 4, 2005.

Chronic renal failure (CRF) is associated with multiple hypothalamic dysfunctions, including reduced secretion of gonadotropin-releasing hormone (GnRH). Because GnRH release is tightly controlled by sympathetic neuronal input, a possible alteration of local noradrenergic neurotransmission in experimental CRF was evaluated. Basal, stimulated, and autoinhibited norepinephrine (NE) release was assessed in hypothalamic and hippocampal tissue slices obtained from 5/6-nephrectomized and control rats. Autoinhibition-free NE release from brain slices, prelabeled with [³H]NE and superfused with physiologic buffer, was stimulated by six electrical pulses, 100 Hz (pseudo-one-pulse stimulation). Autoinhibited NE release was induced by 90 pulses at 3 Hz. The release of tritiated NE was measured upon addition of increasing concentrations of unlabeled NE to exogenously activate the inhibitory ₂-autoreceptor. Although neither basal nor stimulated NE release differed between the groups, significantly lower pIC₅₀ and I_max estimates of the concentration-response curves of exogenous NE on [³H]NE release were observed in CRF rats, suggesting a diminished autoinhibition of hypothalamic noradrenergic terminals in CRF. Western blotting of tissue homogenates disclosed a significantly reduced abundance of ₂-autoreceptor protein in hypothalamic tissue from CRF rats. These abnormalities were selectively observed in the hypothalamus, whereas noradrenergic autoinhibition seemed unaltered in the hippocampus. The results suggest a diminished autoinhibition of hypothalamic NE release in CRF. Although impaired hypothalamic NE autoinhibition does not explain reduced GnRH secretion in CRF, it may be involved in the pathogenesis of sympathetic hyperactivity associated with this condition.

This article has been cited by other articles:

				N. A. Lutaif, E. M. Rocha, L. A.Veloso, L. M. Bento, and J. A. R. Gontijo Renal contribution to thermolability in rats: role of renal nerves Nephrol. Dial. Transplant., December 1, 2008; 23(12): 3798 - 3805. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673