Cardiovascular effects of CDP-choline and its metabolites: involvement of peripheral autonomic nervous system.
Intraperitoneal administration of CDP-choline (200-900 micromol/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 micromol/kg), while it decreased by choline (200-600 micromol/kg) administration; phosphocholine or choline administration (up to 600 micromol/kg) decreased heart rate. Intraperitoneal cytidine monophosphate (200-600 micromol/kg) or cytidine (200-600 micromol/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 alpha-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.
Cansev
Mehmet
M
Department of Pharmacology and Clinical Pharmacology, Uludag University School of Medicine, Gorukle, Bursa 16059, Turkey. mcansev@uludag.edu.tr
Yilmaz
Mustafa Sertac
MS
Ilcol
Yesim Ozarda
YO
Hamurtekin
Emre
E
Ulus
Ismail Hakki
IH
D000311:Adrenal Glands / Q000187:drug effects / Q000294:innervation; D000315:Adrenalectomy; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D002794:Choline / Q000494:pharmacology; D003562:Cytidine / Q000494:pharmacology; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D003568:Cytidine Monophosphate / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018697:Nootropic Agents / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D010767:Phosphorylcholine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D013563:Sympathectomy, Chemical; D014667:Vasopressins / Q000097:blood
D002395:Catecholamines; D018697:Nootropic Agents; D010767:Phosphorylcholine; D014667:Vasopressins; D003566:Cytidine Diphosphate Choline; D003562:Cytidine; D012083:Renin; D003568:Cytidine Monophosphate; D002794:Choline