Cardiovascular effects of CDP-choline and its metabolites: Involvement of peripheral autonomic nervous system


Cansev M. , Yilmaz M. S. , Ilcol Y. O. , Hamurtekin E., Ulus I. H.

European Journal of Pharmacology, vol.577, pp.129-142, 2007 (Journal Indexed in SCI Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 577
  • Publication Date: 2007
  • Doi Number: 10.1016/j.ejphar.2007.08.029
  • Title of Journal : European Journal of Pharmacology
  • Page Numbers: pp.129-142
  • Keywords: CDP-choline, cardiovascular, phosphocholine, choline, cytidine, MUSCARINIC RECEPTORS, REVERSES HYPOTENSION, BLOOD-PRESSURE, ACETYLCHOLINE, RELEASE, RAT, CITICOLINE, STROKE, MICE, DOG

Abstract

Intraperitoneal administration of CDP-choline (200-900 μmol/kg) increased blood pressure and decreased heart rate of rats in a dose- and time-dependent manner. These responses were accompanied by elevated serum concentrations of CDP-choline and its metabolites phosphocholine, choline, cytidine monophosphate and cytidine. Blood pressure increased by intraperitoneal phosphocholine (200-900 μmol/kg), while it decreased by choline (200-600 μmol/kg) administration; phosphocholine or choline administration (up to 600 μmol/kg) decreased heart rate. Intraperitoneal cytidine monophosphate (200-600 μmol/kg) or cytidine (200-600 μmol/kg) increased blood pressure without affecting heart rate. Pressor responses to CDP-choline, phosphocholine, cytidine monophosphate or cytidine were not altered by pretreatment with atropine methyl nitrate or hexamethonium while hypotensive effect of choline was reversed to pressor effect by these pretreatments. Pretreatment with atropine plus hexamethonium attenuated or blocked pressor response to CDP-choline or phosphocholine, respectively. Heart rate responses to CDP-choline, phosphocholine and choline were blocked by atropine and reversed by hexamethonium. Cardiovascular responses to CDP-choline, phosphocholine and choline, but not cytidine monophosphate or cytidine, were associated with elevated plasma catecholamines concentrations. Blockade of α-adrenoceptors by prazosin or yohimbine attenuated pressor response to CDP-choline while these antagonists blocked pressor responses to phosphocholine or choline. Neither bilateral adrenalectomy nor chemical sympathectomy altered cardiovascular responses to CDP-choline, choline, cytidine monophosphate or cytidine. Sympathectomy attenuated pressor response to phosphocholine. Results show that intraperitoneal administration of CDP-choline and its metabolites alter cardiovascular parameters and suggest that peripheral cholinergic and adrenergic receptors are involved in these responses. © 2007 Elsevier B.V. All rights reserved.