Cardiovascular effects of centrally injected melittin in hemorrhaged hypotensive rats: The investigation of peripheral mechanisms


YALÇIN M., SAVCI V.

NEUROPEPTIDES, vol.41, no.6, pp.465-475, 2007 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 6
  • Publication Date: 2007
  • Doi Number: 10.1016/j.npep.2007.07.002
  • Journal Name: NEUROPEPTIDES
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.465-475

Abstract

We have previously shown that centrally injected melittin, a phospholipase A(2) (PLA(2)) activator, increases blood pressure and decreases heart rate in the normotensive conscious rats. In the current study we aimed to determine the cardiovascular effects of melittin in hemorrhaged hypotensive rats and to investigate the mediation of peripheral adrenergic, vasopressinergic and renin angiotensin system in the pressor effect of centrally administrated melittin in both normotensive and hypotensive conditions. Acute hypotensive hemorrhage was performed by withdrawing a total volume of 2.2 ml of blood/100 g body weight over a period of 10 min. Melittin was injected intracerebroventricularly (i.c.v.) at the doses of 1.5 mu g, 3.0 mu g or 6.0 mu g after the stabilization period of hemorrhage procedure. We also repeated previous experiments by injecting melittin (1.5 mu g, 3.0 mu g or 6.0 mu g; i.c.v.) to the normotensive animals. Melittin caused dose- and time-dependent increases in mean arterial pressure (MAP) in normal and hypotensive conditions and decreases in heart rate (HR) in normotensive conscious animals. In hypotensive rats, melittin injected at the dose of 6.0 mu g completely restored the decrease in blood pressure. Plasma adrenaline, noradrenaline, vasopressin levels and renin activity increased after melittin (3.0 mu g; i.c.v) administration in normal conditions. Hemorrhage, itself, produced an increase in these plasma hormone levels and melittin (3.0 mu g; i.c.v.) caused additional increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity in hypotensive conditions. Intravenous pretreatments of rats with prazosin (0.5 mg/kg), an alpha(1), adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Me-Tyr(2)-Arg(8)]-vasopressin (10 mu g/kg), a vasopressin V, receptor antagonist, or saralasin (250 mu g/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to melittin (3.0 mu g; i.c.v.) in both normotensive and hypotensive conditions. Besides, the combined administration of these three antagonists before melittin completely abolished the pressor responses to drug in both conditions.