6-ketoprostaglandin-f1-alpha and Varicose-Veins

Experiments were designed to determine the production of prostacyclin and thromboxane and the activation of cyclic nucleotides in human varicose and nonvaricose veins and to determine whether these second messenger pathways were differentially activated by the venotropic extract of Ruscus aculeatus.. The experiments were designed to characterize the activity of cyclic nucleotides and the production of prostaglandins in human varicose and nonvaricose veins. Segments of the greater saphenous veins and the adjacent tributaries were obtained from patients who underwent vein stripping and excision of primary varicose veins. The saphenous veins from the patients who underwent peripheral arterial bypass grafting were used as controls. The segments of veins were incubated in Krebs-Ringer bicarbonate solution in the presence of venotropic extract of Ruscus aculeatus (10(-3) g/mL) or in water-miscible organic solvent (dimethyl sulfoxide, 10(-3) g/mL), for 1, 5, and 10 minutes at 37 degrees C. The nonspecific phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, 10(-4) g/mL) was used to block cyclic nucleotide degradation in some samples. Tissue and media samples were collected. Tissue concentrations of both cyclic adenosine monophosphate and cyclic guanosine monophosphate (cAMP and cGMP, respectively) and media concentrations of 6-ketoprostaglandin-F(1)(alpha) (the stable metabolite of prostacyclin) and thromboxane B(2) (the stable metabolite of thromboxane A(2)) were measured by means of radioimmunoassay. Cyclooxygenase 2 was measured with Western blot analysis.. The varicose veins showed greater levels of cAMP but not of cGMP at all time points as compared with the control veins. Prostanoid production was not significantly altered in the varicose veins. Stimulation with Ruscus aculeatus increased the cAMP concentration in the varicose veins but did not affect the cGMP levels. The ratio between 6-ketoprostaglandin-F(1)(alpha) and thromboxane B(2) was two-fold greater in the varicose veins as compared with the control veins. In the presence of the extract, the ratio of 6-ketoprostaglandin-F(1)(alpha) and thromboxane B(2) was identical in both types of veins. Cyclooxygenase 2 was not present in either the control or the varicose veins.. These results suggest that cAMP levels are elevated in varicose veins and that they can be altered with drug treatment in varicose veins. This chemical pathway may be considered as a modulatory target to affect contraction with venotropic drugs.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Cyclic AMP; Cyclic GMP; Cyclooxygenase 2; Female; Humans; Isoenzymes; Male; Membrane Proteins; Middle Aged; Peroxidases; Prostaglandin-Endoperoxide Synthases; Saphenous Vein; Second Messenger Systems; Thromboxane B2; Varicose Veins

The concentration of serotonin and prostaglandins in peritoneal fluid were measured in 14 patients with pelvic congestion and 14 normal women. Results showed that in pelvic congestion group 5-HT and TXB2 and 6-keto-PGF1 alpha levels were higher than that of control; but DA and histamine were lower. It is suggested that the serotonin and prostaglandins may play an important role in developing pelvic congestion.

Topics: 6-Ketoprostaglandin F1 alpha; Ascitic Fluid; Dopamine; Fallopian Tubes; Female; Humans; Pelvis; Pregnancy; Serotonin; Sterilization, Tubal; Thromboxane B2; Varicose Veins

Increased urinary metabolites of the antiaggregatory vasodilator prostacyclin (PGI2) and the proaggregatory vasoconstrictor thromboxane A2 (TXA2) have been reported in deep vein thrombosis; however, the tissue(s) of origin is uncertain. Because little is known about the formation of PGI2 or TXA2 from its common precursor, prostaglandin (PG) endoperoxide H2 (PGH2), by varicose veins, we determined the formation of 6-keto-PGF1 alpha (the stable metabolite of PGI2), TXB2 (the stable metabolite of TXA2), and PGE2. Segments of normal saphenous vein and varicose vein (nine and six patients, respectively) were incubated with 10 microM [14C]PGH2 for 2 min at 37 degrees C; products were separated by thin-layer chromatography. Surface area and mass of normal and varicose vascular segments were 19.5 +/- 0.8 versus 18.8 +/- 0.6 mm2 and 11.6 +/- 1.4 versus 10.7 +/- 0.7 mg, respectively. Formation of 6-keto-PGF1 alpha and TXB2 by the segments of varicose vein was significantly increased over that of normal vein: 157 +/- 14 versus 243 +/- 17 pmole of 6-keto-PGF1 alpha (P less than 0.005) and 22 +/- 3 versus 35 +/- 5 pmole of TXB2 (P less than 0.01). The formation of PGE2 by segments of varicose vein was not significantly different from that of normal vein (201 +/- 9 vs 219 +/- 11, respectively). Deoxyribonucleic acid (DNA) content of normal and varicose vein was 1.69 +/- 0.12 and 1.51 +/- 0.13 mg per gram of tissue, respectively. The data suggest that the increased PGI2 formation may reflect increased activity or content of PGI2 synthase. The increase in TXA2 formation may reflect increased productivity or an increased presence of residual platelets or microemboli.

Topics: 6-Ketoprostaglandin F1 alpha; Epoprostenol; Humans; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins H; Thromboxane A2; Thromboxane B2; Varicose Veins

We studied the ability of salicylate to counteract the effect of aspirin on platelet thromboxane synthesis and prostacyclin formation in venous tissue in patients undergoing saphenectomy. A single intravenous dose of 40 mg aspirin completely blocked thromboxane formation and reduced prostacyclin to about 43% of the control values. When salicylate (1000 mg po) corresponding in anesthetized subjects to blood levels of 25.9 +/- 5 micrograms/ml was administered before aspirin, vascular prostacyclin was no longer inhibited, whereas platelet thromboxane was still significantly blocked. These results suggest that the combination of salicylate with aspirin at an appropriate dose ratio may result in almost complete dissociation of the drug's effect on platelets and vessels in man.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aspirin; Blood Platelets; Drug Interactions; Female; Humans; Middle Aged; Salicylates; Salicylic Acid; Thromboxane B2; Varicose Veins; Veins