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

• Published in: Nephrology, dialysis, transplantation Vol. 24; no. 8; pp. 2362 - 2370
• Main Authors: Kuncová, Jitka, Švíglerová, Jitka, Kummer, Wolfgang, Rajdl, Daniel, Chottová-Dvořáková, Magdalena, Tonar, Zbyněk, Nalos, Lukáš, Štengl, Milan
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2009; Oxford Publishing Limited (England)
• Subjects: Adrenergic beta-Antagonists - pharmacology; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; asymmetric dimethylarginine; Atropine - pharmacology; Biological and medical sciences; Blotting, Western; Carbachol - pharmacology; Cardiotonic Agents - pharmacology; Choline O-Acetyltransferase - genetics; Choline O-Acetyltransferase - metabolism; chronic renal failure; Emergency and intensive care: renal failure. Dialysis management; Heart - innervation; Heart Rate - physiology; Intensive care medicine; Kidney - drug effects; Kidney - metabolism; Kidney - surgery; Male; Medical sciences; Metipranolol - pharmacology; Nephrectomy; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Norepinephrine - metabolism; parasympathetic innervation; Parasympathetic Nervous System - drug effects; Parasympathetic Nervous System - physiology; Parasympatholytics - pharmacology; Plasma Membrane Neurotransmitter Transport Proteins - genetics; Plasma Membrane Neurotransmitter Transport Proteins - metabolism; rat heart; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; subtotal nephrectomy; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Vagus Nerve - drug effects; Vagus Nerve - physiology; Vesicular Acetylcholine Transport Proteins - genetics; Vesicular Acetylcholine Transport Proteins - metabolism; parasympathetic innervation; rat heart; subtotal nephrectomy; chronic renal failure; asymmetric dimethylarginine; Kidney disease; Urinary system disease; Rat; Hemodialysis; Rodentia; Subtotal; Heart rate; Extrarenal dialysis; Vertebrata; Mammalia; Nephrectomy; Animal; Renal failure
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfp123

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.