Effects of nicardipine on the ex vivo release of eicosanoids after experimental subarachnoid hemorrhage.
The activation of lipid peroxidation and the enhancement of arachidonic acid metabolism have been demonstrated as indicators of brain damage after subarachnoid hemorrhage (SAH). Meanwhile, the final common pathway of neuronal damage seems to be related to the impaired homeostasis of Ca++. The present study evaluated the effect of the calcium-antagonist nicardipine on arachidonate metabolism after experimental induction of SAH. The ex vivo release of four eicosanoids (prostaglandin (PG)D2, PGE2, 6-keto-PGF1 alpha, and leukotriene (LT)C4) was measured at different intervals after SAH induction. Rats were separated into the following three groups: a sham-operated group, an SAH group (rats were injected with 0.3 ml autologous arterial blood), and an SAH-treated group (after SAH induction, rats were treated with nicardipine 1.2 mg/kg intraperitoneally). Nicardipine significantly decreased the ex vivo release of PGD2 at 48 hours after SAH (p less than 0.01). The release of PGE2 was significantly enhanced at 6 hours after SAH, while in the nicardipine-treated group PGE2 release is significantly reduced. Nicardipine also affects the lipoxygenase pathway, reducing the release of LTC4 at 1, 6, and 48 hours after SAH induction. The results of the present study show that nicardipine treatment exerts an inhibitory effect on both biochemical pathways of arachidonic acid metabolism; aside from vascular effects, nicardipine could exert a protective role against the release of arachidonate metabolites, which could play a significant role in the pathogenesis of brain damage after SAH.
Rodriguez y Baena
R
R
Department of Surgery, (Neurosurgical Section), Policlinico S. Matteo, Italy.
Gaetani
P
P
Marzatico
F
F
Benzi
G
G
Pacchiarini
L
L
Paoletti
P
P
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*
D015777:Eicosanoids; D013189:SRS-A; D015121:6-Ketoprostaglandin F1 alpha; D009529:Nicardipine; D015232:Dinoprostone; D015230:Prostaglandin D2