Centrally administered CDP-choline induced cardiovascular responses are mediated by activation of the central phospholipase-prostaglandin signaling cascade


Topuz B. B. , Altinbas B., İLHAN T. , Yilmaz M. S. , ERDOST H. , Saha S., ...More

Brain Research, vol.1563, pp.61-71, 2014 (Journal Indexed in SCI Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 1563
  • Publication Date: 2014
  • Doi Number: 10.1016/j.brainres.2014.03.040
  • Title of Journal : Brain Research
  • Page Numbers: pp.61-71

Abstract

The present study was designed to determine the involvement of central prostaglandin synthesis on the pressor and bradycardic effect of cytidine 5′-diphosphocholine (CDP-choline). Intracerebroventricular (i.c.v.) administration of CDP-choline was made and blood pressure and heart rate were recorded in male Sprague Dawley rats throughout this study. Microdialysis and immunohistochemical studies were performed to measure extracellular total prostaglandin concentration and to show cyclooxygenase-1 and-2 (COX-1 and-2) immunoreactivities, respectively, in the posterior hypothalamic area. Moreover, rats were pretreated (i.c.v) with mepacrine [a phospholipase A2 (PLA2) inhibitor], ibuprofen [a nonselective COX inhibitor], neomycine [a phospholipase C (PLC) inhibitor] or furegrelate [a thromboxane A2 (TXA2) synthesis inhibitor] 5 min prior to the injection of CDP-choline to determine the effects of these inhibitors on cardiovascular responses to CDP-choline. Control rats were pretreated (i.c.v) with saline. CDP-choline caused a dose-and time-dependent increase in blood pressure and decrease in heart rate. Immunohistochemical studies showed that CDP-choline increased COX-1 and-2 immunoreactivities in the posterior hypothalamic area. CDP-choline also elevated hypothalamic extracellular total prostaglandin concentration by 62%, as shown in microdialysis studies. Mepacrine or ibuprofen pretreatments almost completely blocked the pressor and bradycardic responses to CDP-choline while neomycine or furegrelate partially attenuated the drug-induced cardiovascular effects. The results suggest that CDP-choline may stimulate prostaglandin synthesis through the activation of PLA2, cyclooxygenases (COX-1 and-2) and prostaglandins and at least TXA2, may mediate the drug's cardiovascular effects. © 2014 Elsevier B.V.