RESUMEN
The effect of indomethacin (10 mg.kg-1 i.p.) on frontal cerebral blood flow has been investigated in male Sprague Dawley rats using the hydrogen clearance technique. Indomethacin elicited a marked reduction in cerebral blood flow in awake free-moving animals. The response to indomethacin was prevented by pretreatment with pentobarbital (50 mg X kg-1, i.p.). On the other hand, indomethacin was able to antagonize the cerebral vasodilation due to apomorphine chlorhydrate (2 mg X kg-1, i.p.), dexamphetamine tartrate (3 mg X kg-1, i.p.) or immobilization stress. Taken together, the above results lead to the suggestion that indomethacin can suppress the coupling of cerebral blood flow to brain metabolism. Further investigations are needed to ascertain whether this uncoupling influence is related to brain cyclooxygenase inhibition.
Asunto(s)
Encéfalo/metabolismo , Circulación Cerebrovascular/efectos de los fármacos , Indometacina/farmacología , Anestesia , Animales , Apomorfina/antagonistas & inhibidores , Dextroanfetamina/antagonistas & inhibidores , Inmovilización , Indometacina/antagonistas & inhibidores , Masculino , Pentobarbital/farmacología , Ratas , Ratas EndogámicasRESUMEN
Indomethacin (10n mg/kg i.p.) induced a marked decrease in local cerebral blood flow (l.CBF), which was measured in the frontal cortex of unanesthetized rats by the hydrogen clearance technique. Brain prostaglandins (PGD2, PGE2, PGF2 alpha,) and 6kPGF1 alpha the stable metabolite of prostacyclin, were significantly decreased. Treatments with inhibitors of lipoxygenase (BW 755C and nordihydroguaiaretic acid) and with FPL 55712, a leukotriene receptor antagonist, did not influence the effect of indomethacin on 1.CBF. The results suggest that the release of vasoconstrictory leukotrienes does not play a major role in the lowering of 1.CBF by indomethacin.