[In vitro oxidation of low density lipoproteins in patients after ischemic stroke]. / Utlenianie in vitro lipoprotein niskiej gestosci u osób po przebytym niedokrwiennym udarze mózgu.

The aim of this work was the evaluation of low density lipoprotein (LDL) susceptibility to oxidation in the survivors of ischaemic stroke. The investigations were performed in 65 individuals at least three months after the onset of acute symptoms. In 24 patients stroke was caused by alterations in main cerebral arteries, in 19 by considerable narrowing of carotid artery, in 15 by alterations in small cerebral arteries with often accompanying hypertension and/or diabetes (lacunar stroke) and in 7 by embolism of cardiac origin in individuals with cardiac arrhythmia and coronary artery disease. The control group comprised 25 age matched persons without pathological symptoms. Plasma lipids and apolipoprotein B levels were determined as well as two antioxidants: alpha-tocopherol level and superoxide dismutase activity. The evaluation of lipid peroxidation was performed by determining thiobarbituric acid reacting substances (TBARS) and lipid peroxides (LPO) increase after 5 hours oxidation of isolated LDL in vitro in the presence of copper ions. The level of IgG directed against modified LDL was also evaluated. In the patients decreased HDL cholesterol level was observed as well as increased apolipoprotein B. In the group of thrombotic strokes high triglycerides were observed. alpha-tocopherol level was decreased in the group of cerebral strokes. The amounts of oxidation products did not differ between the whole group of patients after stroke and the controls. A significant increase concerned only the group of lacunar strokes. The evaluation of LDL susceptibility to oxidation in patients after stroke by measuring absorption at 234 nm and determining the time period necessary to the onset of intensive LDL oxidation will be the subject of a separate publication.

Release of prostaglandin E-like material from perfused mesenteric blood vessels of rabbits.

Infusions of noradrenaline (1-3 mug ml(-1) min(-1)) into the mesenteric vascular preparation of the rabbit caused a 2 to 5 fold rise in perfusion pressure and a release of prostaglandin E-like material (3.23 +/- 0.65 (s.e.) ng PGE2 equivalents ml(-1)). Indomethacin (3 mug ml(-1)) prevented whereas arachidonic acid (0.2 mug ml(-1)) augmented, the noradrenaline-evoked release of a prostaglandin E-like material. The walls of arterioles or precapillary vessels are the proposed site of prostaglandin generation.

Regulatory role of prostaglandins in the vascular system.

It is reported that noradrenaline-induced vasoconstriction initiates generation of prostaglandins of the E series by vasculas walls. These endogenous prostaglandins attenuate the vasoconstrictor effect of noradrenaline. Inhibitors of prostaglandin biosynthesis (indomethacin, mefenamic acid) abolish acute tolerance to noradrenaline infusions and counteract hypotension which is induced in cats by injection of endotoxin or by injection of rat blood.

Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig.

Infusion of norephinephrine (NE) (1 - 3 mug/ml/min) into the isolated mesenteric vascular preparation of rabbit resulted in a rise in perfusion pressure, which was associated with the release of prostaglandin E-like substance (PGE) at a concentration of 2.81 +/- 0.65 ng/ml in terms of PGE2. Indomethacin (3 mug/ml) abolished the NE-induced release of PGE. Arachidonic acid (0.2 mug/ml) in the presence of indomethacin did not restore the NE-induced release of PGE. Hydrocortisone (10 - 30 mug/ml) and dexamethasone (2 - 5 mug/ml) also inhibited the NE-induced release of PGE. The inhibitory action of both corticosteroids was abolished by arachidonic acid (0.2 mug/ml). Antigen-induced release of a prostaglandin-like substance (PGs) (43.1 +/- 3.8 ng/ml in terms of PGE2 and a rabbit aorta contracting substance (RCS) from perfused lungs of sensitized guinea pigs was completely abolished by indomethacin (5 mug/ml) or by hydrocortisone (100 mug/ml). Indomethacin, however, increased histamine release up to 280% of the control level, which was 470 +/- 54 ng/ml, while hydrocortisone diminished histamine release down to 30% of the control level. A superimposed infusion of arachidonic acid (1 mug/ml) into the pulmonary artery reversed the hydrocortisone-induced blockade of the release of RCS and PGs. It may be concluded that corticosteroids neither inhibit prostaglandin synthetase nor influence prostaglandin transport through the membranes but they do impair the availability of the substrate for the enzyme.

The dual action of meclofenamate on the contractile response to PGF2 alpha in the guinea-pig trachea.

Indomethacin and meclofenamate (1 mug/ml) enhance contractile action of PGF2 alpha (5-20 mug) in guinea-pig tracheas superfused with Tyrode solution (5 ml/min). Unlike indomethacin, meclofenamate at a concentration of 10 mug/ml antagonizes contractions of guinea-pig tracheas produced by PGF2 alpha (5-20 mug), while the contractile action of histamine (0-5-2-0 mug) is enhanced. It is concluded that low concentrations of meclofenamate (1 mug/ml) inhibit prostaglandin biosynthesis in tracheal smooth muscles and therefore contractile action of exogenous PGF2 alpha is enhanced, while meclofenamate at a high concentration (10 mug/ml) blocks the receptor sites for PGF2 alpha.

Generation of prostaglandin E-like material by the guinea-pig trachea contracted by histamine.

Challenges of the superfused (1 ml min-1) trachea with histamine (100-200 mug) result in the release of prostaglandin E-like material (3-25 ng in terms of prostaglandin E2) but no prostaglandin F-like activity has been detected in the superfusate. This release is blocked by indomethacin (1mug ml-1) and then the contractile action of histamine is enhanced. It is concluded that the release of a prostaglandin E-like material by histamine from tracheal smooth muscles is a self-defensive mechanism protecting against the strong constriction of airways. The maximal relaxation of trachea by isoprenaline (50-500 mug) is not accompanied by the release of a prostaglandin-like material.