thromboxane-a2 and Intracranial-Arteriosclerosis

Topics: Animals; Epoprostenol; Humans; Intracranial Arteriosclerosis; Microsomes; Platelet Aggregation; Prostaglandins; Rabbits; Rats; Thrombosis; Thromboxane A2; Thromboxanes

It is shown that in patients with cerebral circulatory disorders, the prostacyclin -thromboxane balance is replaced toward the latter one. As a result of nifedipine administration part of the test subjects demonstrate a rise of the content of prostacyclin and a decline of the concentration of thromboxane. This effect of nifedipine is ascertained to be in a good agreement with its action on blood inflow to the brain and platelet aggregation. It is concluded that the efficacy of nifedipine can be raised if it is combined with the drugs that enhance the synthesis of prostacyclins in the body.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Aged; Cerebral Infarction; Cerebrovascular Circulation; Epoprostenol; Humans; Intracranial Arteriosclerosis; Middle Aged; Nifedipine; Thromboxane A2

Prostacyclin (PGI2) and thromboxane A2 (TxA2) formation by whole-tissue segments of nine carotid endarterectomy specimens (CES), five normal aortic specimens (NAS), six saphenous vein specimens (SVS), and four platelet samples were determined by incubation with 10 mumol/L 1-14C-radiolabeled prostaglandin endoperoxide H2 (PGH2), and in other experiments with and without 10 mumol/L of CGS 13080, a TxA2 synthase inhibitor. PGI2 formation (expressed as picomoles 6-keto-PGF1 alpha/2-min incubation per sample) by nonatheromatous proximal intima of CES (307 +/- 23, mean +/- standard error) and distal intima of CES (260 +/- 22) was not statistically different; however, it was greater than atheromatous transitional plaque (159 +/- 13 pmol) (p less than 0.01) and ulceration regions (140 +/- 15 pmol) (p less than 0.01) of CES, NAS (204 +/- 16 pmol) (p less than 0.01), and SVS (165 +/- 9 pmol) (p less than 0.01). TxA2 formation (expressed as picomoles TxB2/2-min incubation per sample) by CES ulceration (51 +/- 2 pmol) was low but greater than proximal (17 +/- 2 pmol) (p less than 0.01), distal (19 +/- 3 pmol) (p less than 0.01), and transitional (23 +/- 3 pmol) (p less than 0.01) regions. TxA2 formation by NAS and SVS was not detected (less than 10 pmol). CGS 13080 inhibited TxA2 formation by CES below the limits of detection. Incubation of 1.9 x 10(5) intact platelets with 10 mumol/L of PGH2 formed a quantity of TxA2 equal to that of CES ulceration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aorta; Blood Platelets; Carotid Arteries; Carotid Artery Diseases; Epoprostenol; Humans; In Vitro Techniques; Intracranial Arteriosclerosis; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins H; Saphenous Vein; Thromboxane A2

The ability of platelets to synthetise thromboxane B2 and hydroxylated fatty acids from arachidonic acid was studied simultaneously with arachidonic acid-induced aggregation in 42 patients suffering from severe cerebral atherosclerosis and also in 34 healthy controls. Additionally, phospholipase-A2-induced aggregation was performed as a probe for arachidonic acid located at the platelet surface. All the assays were performed with washed platelets, eliminating a possible influence of plasma. Platelets from patients were found responsive to significantly lower concentrations of arachidonic acid whereas thromboxane and hydroxylated fatty acid biosynthesis did not differ from controls. In the experimental conditions used, 75% of the control platelets underwent aggregation with phospholipase A2 plus sphingomyelinase C, in comparison to only 50% for the patients, indicating the necessity for further analysis of the platelet membrane lipids in atherosclerosis.

Topics: Adult; Aged; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Fatty Acids; Female; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Phospholipases A; Phospholipases A2; Platelet Aggregation; Thromboxane A2