The role of the central thromboxane A2 in cardiovascular effects of a phospholipase A2 activator melittin administrated intracerebroventricularly in normotensive conscious rats

The current study was designed to determine the cardiovascular effect of centrally administrated melittin, a phospholipase A(2) (PLA(2)) activator, and the mediation of central thromboxane A(2) (TXA(2)) and its receptors in normotensive conscious rats. Studies were performed in normotensive male Sprague Dawley rats injected intracerebroventricularly (i.c.v.) with melittin. Melittin (1.5, 3.0, 6.0 mu g/5.0 mu l; i.c.v.) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR). Maximal effects were observed 5-10 min after 3.0 mu g dose of melittin. In order to test the mediation of central TXA(2) and its central receptors in the cardiovascular effect of melittin, the rats were pretreated with furegrelate (500.0 mu g; i.c.v.), a TXA(2) synthesis inhibitor, and SQ-29548 (8.0 mu g; i.c.v.), a TXA(2) receptor antagonist, 15 min prior to melittin (3.0 mu g). Furegrelate or SQ-29548 partially inhibited the pressor effect and bradycardia elicited by melittin. In conclusion, our findings show that centrally administered melittin increases MAP and decreases HR in conscious rats. Moreover, according to our findings, central TXA(2) and its receptors may in part mediate melittin-induced cardiovascular effects. (c) 2006 Elsevier Ltd. All rights reserved.