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NDT Advance Access published online on March 25, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp123
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Parasympathetic regulation of heart rate in rats after 5/6 nephrectomy is impaired despite functionally intact cardiac vagal innervation

Jitka Kuncová1, Jitka Svíglerová1, Wolfgang Kummer2, Daniel Rajdl3, Magdalena Chottová-Dvoráková1, Zbynek Tonar4, Lukás Nalos1 and Milan Stengl1

1 Department of Physiology, Charles University in Prague, Faculty of Medicine in Plzen, Lidická 1, 30100 Plzen, Czech Republic 2 Institute for Anatomy and Cell Biology, Justus-Liebig-University, Aulweg 123, 35385 Giessen, Germany 3 Faculty of Medicine and Teaching Hospital in Plzen, Institute of Clinical Biochemistry and Hematology, Charles University in Prague, alej Svobody 80, 30460 4 Faculty of Medicine in Plzen, Department of Histology and Embryology, Charles University in Prague, Karlovarská 48, 30100 Plzen, Czech Republic

Correspondence and offprint requests to: Jitka Kuncová; E-mail: jitka.kuncova{at}lfp.cuni.cz



  Abstract

Background. Chronic renal failure is frequently associated with a high risk of sudden cardiac death due to dysfunction of the autonomic nervous system. The pathogenic mechanisms underlying the parasympathetic cardiac dysautonomia are not fully elucidated yet.

Methods. Chronic renal failure was induced in rats by 5/6 nephrectomy. Blood pressure, resting heart rate and plasma levels of creatinine, urea and asymmetric dimethylarginine (ADMA) were measured. To characterize the parasympathetic innervation of the heart, chronotropic responses to atropine, metipranolol and to vagal stimulation in the absence or presence of ADMA were investigated in vivo. In vitro, chronotropic and inotropic effects of carbachol and ADMA and mRNA expression of muscarinic M2 receptors, high affinity choline transporter (CHT1), vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) were assessed in the isolated cardiac tissues.

Results. In 5/6 nephrectomy rats, the resting heart rate was significantly higher and the parasympathetic tone, measured as the effect of atropine after administration of metipranolol was significantly lower than in control animals. Plasma ADMA levels were significantly elevated in the uraemic rats and significantly inversely correlated with the effect of atropine on the heart rate. No differences were revealed in the plasma norepinephrine concentrations, negative chronotropic responses to stimulation of the vagus nerves, chronotropic and inotropic responses to carbachol and the relative expression of M2 receptors, CHT1, VAChT and ChAT.

Conclusion. The data suggest that cardioacceleration in chronic renal failure is caused by a diminished cardiac parasympathetic tone in the presence of a functionally intact intrinsic cardiac cholinergic signalling system.

Keywords: asymmetric dimethylarginine; chronic renal failure; parasympathetic innervation; rat heart; subtotal nephrectomy

Received for publication: 17. 6.08
Accepted in revised form: 2. 3.09


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