Prostaglandin release from isolated rabbit cerebral cortex micro-vessels--comparison of 6-keto PGF1 alpha and PGE2 release from micro-vessels incubated in 100% O2, room air and 95% N2:5% CO2.

Abstract

SUMMARY Prostaglandin release from microvessels isolated from the rabbit cerebral cortex was determined under three different atmospheric conditions: 100% O 2 ("O 2 ") room air, and 95% N 2 =5% CO 2 ("N 2 -COj"). Initial studies with homogenates prepared from rabbit cerebral microvessels (RCMV) indicated two pathways of enzymatic PGH 2 transformation, namely PGI 2 synthase and GSH-dependent PGH-PGE isomerase. We measured the release of the principal products of these pathways, 6-keto PGF |a and PGE, from freshly prepared RCMV. The release of 6-keto PGF |a exceeded that of PGE^ in all three protocols. RCMV incubated in "N 2 -CO 2 " exhibited a reduction in the release of 6-keto PGF la compared to room air or "O 2 " incubated RCMV, evident at 30-60 min of incubation. No significant differences in the release of PGE 2 were observed among the three incubation protocols. In all three incubation protocols the ratio of 6-keto PGF |a to PGE 2 did not differ during the initial 10 minutes of each incubation. After 30 to 60 min of incubation, this ratio did not change from the "O 2 " or room air treated RCMV, but decreased significantly for the "N 2 -CO 2 " treated group. To determine the reversibility of the apparent "N 2 -CO 2 " induced decline in 6-keto PGF |a release, microvessels were removed from the nitrogen atmosphere and incubated in room air. Release was measured during the initial 10 min following reintroduction to room air and was compared to room air pretreated controls treated in an identical manner. Complete recovery of 6-keto PGF |a production was observed, and an enhanced ratio of 6-keto PGF lo to PGE 2 observed in the "N 2 -CO 2 " treated RCMV. In view of the opposing actions of PGI 2 (vasodilator) and PGE 2 (mild vasoconstrictor) on cerebrovascular tone, this study suggests that release of prostaglandins by the microvasculature may participate in the cerebrovascular response to ischemia. In addition, this study suggests that the release of 6-keto PGF |n and PGE 2 by cerebral microvessels may be regulated independently.Stroke Kenzie 9 have shown that injection of indomethacin in baboon induces a decrease in CBF, proposed by these authors to be due to inhibition of prostacyclin synthesis by vascular endothelium. Pickard and Mackenzie 9 also demonstrated a reduction in the CBF response under hypercapnic conditions when indomethacin is administered. However, a recent study by Wennmalm and co-workers 10 indicates the effects of indomethacin on basal and hypercapnic CBF (in man) is not due to the effects of indomethacin on PGI 2 (or other prostaglandins) synthesis and release in the cerebral circulation. In this study, these authors compared the effects of indomethacin, naproxen and aspirin on CBF under basal and hypercapnic conditions. Administration of all three drugs eliminated arachidonic acid induced platelet aggregation in platelets obtained from the treated patients. Only indomethacin, and only when given acutely, elicited a decrease in CBF under basal or hypercapnic conditions. Additionally, these auth...

Deteriorating stroke model: histopathology, edema, and eicosanoid changes following spinal cord ischemia in rabbits.

“…26 On consumption of much of the AA, PGEisomerase activity is resumed, leading to PGE 2 generation as seen 30 minutes after reperfusion. Since PGE 2 has constrictor effects on rabbit CNS microvessels, 13 elevated PGE 2 levels may propagate the initial vasoconstriction produced by TxA 2 . The imbalance in the TxA 2 : PGI 2 ratio could favor platelet aggregation and vasoconstriction, thus leading to further ischemic damage.…”