Synthesis of prostaglandins and thromboxane B2 by cerebral arteries.

Abstract

SUMMARYThe capacity of cerebral arteries to synthesize prostaglandins was studied by 2 procedures. In one, bovine cerebral arteries were incubated with 0.1 nC (lu C)-arachidonic acid for 3 hours. Using thin layer chromatography, 5 products of this arachidonic acid were isolated: prostaglandin E^ (PGE 2 ), prostaglandin F 2o (PGF 2o ), 6-keto prostaglandin F lo (6-keto PGF la ), prostaglandin D 2 (PGD 2 ), and thromboxane B 2 (TxB 2 ). In the second group of experiments the biosynthesis of these lipids from endogenous substrate was confirmed, except for PGD 2 , by means of gas liquid chromatography-mass spectroscopy. In addition, the production of PGE 2 and PGF 2a was quantified. An average of 196 ng PGF^ and 172 ng PGF 2a were synthesized per gram tissue in one hour. Meclofenamate inhibited the formation of these 2 prostaglandins while serotonin stimulated synthesis approximately 20-25%. The present finding demonstrates that cerebral arteries form several prostaglandins and, likely, thromboxane B 2 . It is hypothesized that these lipids may play a role in the vasomotion of cerebral blood vessels in health and disease. The relative rates of synthesis of these lipids may be important for maintaining normal cerebral circulation. However, in cerebrovascular disease the normal balance between the rate of synthesis of those prostaglandins which constrict and those which dilate may be disturbed.

Effect of indomethacin on cerebral blood flow, carbon dioxide reactivity and the response to epoprostenol (prostacyclin) infusion in man.

“…However, within each treatment group, PGI2 infusion caused a small rise in heart rate, mean increase 9*4 beats/min on placebo, 6 The current study has also demonstrated that pretreatment with oral indomethacin does not alter the normal cerebrovascular response to an increase in arterial pCO2. This is in contrast to the conclusions of two previous studies, which have suggested that indomethacin reduces cerebral vasodilation during hypercapnia in man3 and the baboon.2 However, both these studies examined the effects of acute administration of indomethacin, rather than two days pretreatment, and this may explain the results.…”

“…Prostacyclin (epoprostenol, PGI2) appeared to have the required characteristics. It is formed by vascular endothelium4 and can be produced in vitro by cerebral vessels.5 6 Blood pressure was recorded from the left arm with a standard mercury sphygmomanometer and the pulse rate measured over 30 seconds from the radial pulse on three occasions during the CBF measurement. Arterial partial pressure of carbon dioxide (pCO2) was estimated by monitoring expiratory CO concentration with a Datex CD 300 infra red analyser.…”

Mechanisms of relaxant action of nicardipine, a new Ca++-antagonist, on isolated dog cerebral and mesenteric arteries.

“…Stroke Vol 14, No 2, 1983 CHEMICAL FACTORS OF THE PATHOGENESIS of cerebral vasospasm following subarachnoid hemorrhage include serotonin, 1-3 catecholamines 4 " 6 and prostaglandins [7][8][9] that are released from the subarachnoid hematoma 10 " and cerebral vessel. 7,812 These substances produce contractions of cerebral and extracerebral vessels by increasing the release of Ca + + from intracellular storage sites and the transmembrane influx of Ca + + .…”

Cerebral ischemia in young patients: it is associated with mitral valve prolapse and abnormal platelet activity in vivo?

“…The present results support the hypothesis that cerebral infarction and TIA in young patients may coincide with an abnormal platelet activity in vivo, and thus support the present therapeutic use of antiplatelet drugs. However, non-steroidal antiflammatory drugs such as aspirin or sulphinpyrazone may not only inhibit the arachidonic acid metabolism in platelets, but also reduce prostaglandin and thromboxane synthesis of the cerebral vasculature 39 and the brain tissue. 40 " 42 The altered platelet activity in vivo may be a transient phenomenon at least for different pathogenetic mechanisms: The observation of an increase of /3-TG and platelet factor 4 in patients with focal migraine at the time of their attacks supports such an assumption 43 and indicates the possibility that activation of platelets in vivo could be related to transient spasms of cerebral blood vessels, a subject to be studied in the future.…”