Cansev Mehmet, Yilmaz Mustafa Sertac, Ilcol Yesim Ozarda, Hamurtekin Emre, Ulus Ismail Hakki
Department of Pharmacology and Clinical Pharmacology, Uludag University School of Medicine, Gorukle, Bursa 16059, Turkey.
Eur J Pharmacol. 2007 Dec 22;577(1-3):129-42. doi: 10.1016/j.ejphar.2007.08.029. Epub 2007 Aug 28.
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.
腹腔注射胞磷胆碱(200 - 900微摩尔/千克)可使大鼠血压升高、心率降低,且呈剂量和时间依赖性。这些反应伴随着血清中胞磷胆碱及其代谢产物磷酸胆碱、胆碱、胞嘧啶单磷酸和胞嘧啶浓度的升高。腹腔注射磷酸胆碱(200 - 900微摩尔/千克)可使血压升高,而注射胆碱(200 - 600微摩尔/千克)则使血压降低;注射磷酸胆碱或胆碱(高达600微摩尔/千克)可使心率降低。腹腔注射胞嘧啶单磷酸(200 - 600微摩尔/千克)或胞嘧啶(200 - 600微摩尔/千克)可使血压升高,但不影响心率。用硝酸甲基阿托品或六甲铵预处理不会改变对胞磷胆碱、磷酸胆碱、胞嘧啶单磷酸或胞嘧啶的升压反应,而这些预处理可将胆碱的降压作用逆转为升压作用。阿托品加六甲铵预处理分别减弱或阻断了对胞磷胆碱或磷酸胆碱的升压反应。对胞磷胆碱、磷酸胆碱和胆碱的心率反应被阿托品阻断,并被六甲铵逆转。对胞磷胆碱、磷酸胆碱和胆碱的心血管反应与血浆儿茶酚胺浓度升高有关,但对胞嘧啶单磷酸或胞嘧啶的心血管反应则不然。哌唑嗪或育亨宾阻断α - 肾上腺素受体可减弱对胞磷胆碱的升压反应,而这些拮抗剂可阻断对磷酸胆碱或胆碱的升压反应。双侧肾上腺切除术或化学性交感神经切除术均未改变对胞磷胆碱、胆碱、胞嘧啶单磷酸或胞嘧啶的心血管反应。交感神经切除术减弱了对磷酸胆碱的升压反应。结果表明,腹腔注射胞磷胆碱及其代谢产物可改变心血管参数,并提示外周胆碱能和肾上腺素能受体参与了这些反应。