title: Central mechanism underlying pressor and bradycardic effect of intracerebroventricularly injected arachidonic acid.
abstract: The aim of the current study was to determine the central cyclooxygenase (COX) pathway and central thromboxane signaling in the cardiovascular effects evoked by arachidonic acid (AA). As a main control for the study, different doses of AA (75, 150, or 300 µg) were administered intracerebroventricularly (i.c.v.). Centrally injected AA dose- and time-dependently increased mean arterial pressure and decreased heart rate in conscious normotensive Sprague-Dawley rats. The maximal cardiovascular effects of AA were observed at min 10 of the injection and lasted almost 30 min. To investigate the central mechanism of the AA-induced cardiovascular effect in conscious normotensive animals, pretreatment with nonselective COX inhibitor indomethacin (200 µg; i.c.v.), thromboxane A2 (TXA2) synthesis inhibitor furegrelate (250 or 500 µg; i.c.v.), or TXA2 receptor antagonist SQ-29548 (8 or 16 µg; i.c.v.) was carried out 15 min before AA (150 µg; i.c.v.) injection. While indomethacin completely prevented the pressor and bradycardic responses to AA, furegrelate and SQ-29548 attenuated these effects in part in awake normotensive rats. In conclusion, these findings suggest that the pressor and bradycardic cardiovascular effects of centrally injected AA are dependent on COX activity being totally central and the TXA2 signaling pathway being subsequently central, at least in part.
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey. muraty@uludag.edu.tr
authors.forename: Murat
authors.initials: M
authors.lastname: Yalcin
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D005231:Fatty Acids, Unsaturated; D006339:Heart Rate / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D057967:Infusions, Intraventricular; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001572:Benzofurans; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D016718:Arachidonic Acid; D013928:Thromboxane A2; C045749:SQ 29548; D011451:Prostaglandin-Endoperoxide Synthases; C039936:furegrelate; D007213:Indomethacin