Centrally administered CDP-choline induced cardiovascular responses are mediated by activation of the central phospholipase-prostaglandin signaling cascade.
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.
Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey.
Bora B
BB
Topuz
Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey.
Burcin
B
Altinbas
Department of Histology and Embryology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey.
Tuncay
T
Ilhan
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Uludag University, Bursa 16059, Turkey.
Mustafa S
MS
Yilmaz
Department of Histology and Embryology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey.
Hatice
H
Erdost
Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK.
Sikha
S
Saha
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Uludag University, Bursa 16059, Turkey.
Vahide
V
Savci
Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey. Electronic address: mrtylcn75@gmail.com.
Murat
M
Yalcin
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D010740:Phospholipases / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D011453:Prostaglandins; D003566:Cytidine Diphosphate Choline; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases
Blood pressure; CDP-choline; Cyclooxygenase; Heart rate; Immunohistochemistry; Microdialysis; Phopspholipase A(2); Phopspholipase C; Prostaglandins