Indomethacin and cerebrovascular permeability to albumin in acute hypertension and cerebral embolism in the rat

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Abstract
The experiments were performed to determine if indomethacin, a prostaglandin synthesis inhibitor, could reduce albumin extravasation and brain edema in some models of blood-brain barrier dysfunction. The blood pressure was increased by i.v. adrenaline or bicuculline in conscious rats with indwelling catheters in the aorta and jugular vein. 125I-labeled serum albumin and Evans blue-albumin were used as tracers of the blood-brain barrier function. Pretreatment with indomethacin significantly reduced albumin extravasation after the administration of adrenaline but not after bicuculline, i.e. when acute hypertension was combined with a metabolically mediated cerebral vasodilatation. It is argued that the protective effect of indomethacin in adrenaline-induced hypertension probably is related to the vasoconstrictory effect of the drug. Five μl of air or Lipiodol were injected into the right internal carotid artery in rats anesthetized with pentobarbitone. The albumin content in the injected hemisphere was seven to nine times higher after fat than after air embolism. No significant reduction of tracer extravasation was obtained in rats treated with indomethacin. Rats subjected to fat embolism had a significant homolateral cerebral edema (i.e. increased water content) which was not reduced by pretreatment with indomethacin. By contrast, the water content was significantly increased also in the non-injected side in rats given indomethacin indicating a larger spread of edema fluid in these animals.