thromboxane-b2 and baicalein

The plasma expression levels of ET-1, TXB2, 6-keto-PGF1alpha, vWF at different time after cerebral ischemia were assayed for observing the effects of baicalin, jasminoidin, cholalic acid, hydrolysis fluid of nacre and the combined prescription (CP) on cerebral vasoconstriction and endothelial cells in MCAO rats.. The plasma levels of ET-1, TXB2, 6-keto-PGF1alpha in MCAO rats were detected by the method of RIA and the plasma expressions of vWF were observed by ELISA.. The levels of ET-1, TXB2/6-keto-PGF1alpha and vWF all increased at different time after cerebral ischemia, so do TXB2 at 12 hours after ischemia. The expression of 6-keto-PGF1alpha significantly reduced at different time point after ischemia in MCAO rat. There were no significant changes after medicine treating 12 hours except baicalin's increasing 6-keto-PGF1alpha level. Jasminoidin and CP significantly reduced the expression of ET-1 at 24 hours after ischemia, so do all effective components except CP on expression of TXB2 at 12 hours after ischemia. The expression of TXB2 was significantly decreased by baicalin and CP at 24 hours after cerebral ischemia. Both baicalin and cholalic acid significantly increased the expression of 6-keto-PGF1alpha at 12 hours after ischemia while cholalic acid and hydrolysis fluid of nacre increased its level after ischemia for 24 hours. TXB2/6-keto-PGF1alpha ratio was reduced distinctively by baicalin, jasminoidin, cholalic acid, CP at the point of 12 hours, while decreased by baicalin and CP, and increased by jasmionoidin at the point of 24 hours. On the other hand, baicalin, hydrolysis fluid of nacre significantly reduced and jasminoidin increased the expression of vWF at the point of 12 hours. At the point of 24 hours, expression of vWF reduced by hydrolysis fluid of nacre and increased by baicalin.. The higher plasma expression of ET-1, TXA2 in plasma aggravated cerebral vasoconstriction and damaged endothelial cells. At the same time, the effective components of "Qing Kai Ling" inhibit the expression of ET-1 , TXA2 and reduce both TXB2/6-keto-PGF1alpha ratio and level of vWF. As a result, they relax cerebral microvessel and protect endothelial cells by different pathway at different target points.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain Ischemia; Cholic Acid; Drugs, Chinese Herbal; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Flavanones; Male; Rats; Rats, Sprague-Dawley; Thromboxane B2; Time Factors; von Willebrand Factor

Isoprostaglandin F(2alpha) type-III (formerly known as 8-iso-prostaglandin F(2alpha)) is produced in large quantities in vivo in clinical situations associated with oxidant stress such as atherosclerosis, hypercholesterolemia, and myocardial reperfusion. Isoprostaglandin F(2alpha) type-III may alter smooth muscle and platelet functions. The aim of this study was to evaluate the effects of isoprostaglandin F(2alpha) type-III on isolated human internal mammary arteries, and to characterise the signalling underlying mechanisms. In organ baths, concentration-dependent contractions of human internal mammary arteries were obtained in response to isoprostaglandin F(2alpha) type-III stimulation. The responses to isoprostaglandin F(2alpha) type-III were inhibited in a concentration-dependent manner by the thromboxane A(2) receptor antagonist, GR 32191 ([1R-[1 alpha(Z), 2beta,3beta,5 alpha(+)-7-[[1, 1'-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1-piperidinyl) cyclo pentyl]-4-4heptanoic acid], hydrochloride), 3x10(-9) to 3x10(-7) M). However, this effect was associated with a decreased maximal contraction. AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid, 10(-6) to 3x10(-5) M), an EP(1)-DP receptor antagonist had no effect on isoprostaglandin F(2alpha) type-III-induced contractions. The maximal responses to isoprostaglandin F(2alpha) type-III were significantly reduced in the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) (E(max): 147+/-20% vs. 213+/-19% in control group, P<0.05). Isoprostaglandin F(2alpha) type-III stimulated thromboxane B(2) release (5.7-fold increase) from human internal mammary arteries. Baicaleine, a non-specific lipoxygenase inhibitor, (10(-4) M) and AA 861 (2,3,5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1,4 benzoquinone), a 5-lipoxygenase inhibitor (10(-5) M) did not affect isoprostaglandin F(2alpha) type-III response. In conclusion, this study shows that (1) isoprostaglandin F(2alpha) type-III is a vasoconstrictor in human internal mammary arteries, with a potency equivalent to prostaglandin F(2alpha), (2) the contractions induced by isoprostaglandin F(2alpha) type-III are mediated by TP receptor but not EP(1)-DP-receptor activation, (3) thromboxane A(2) but not cysteinyl leukotrienes production is involved in the vascular effects of isoprostaglandin F(2alpha) type-III. Isoprostaglandin F(2alpha) type-III, produced at sites of free radical generation, may play an important role in internal mammary artery spasm in situatio

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Aged; Benzoquinones; Biphenyl Compounds; Dinoprost; Dose-Response Relationship, Drug; F2-Isoprostanes; Female; Flavanones; Flavonoids; Heptanoic Acids; Humans; In Vitro Techniques; Leukotrienes; Lipoxygenase Inhibitors; Male; Mammary Arteries; Middle Aged; Prostaglandin Antagonists; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP1 Subtype; Receptors, Thromboxane; Thromboxane B2; Vasoconstriction; Vasoconstrictor Agents; Xanthenes; Xanthones

This study investigated, in isolated human internal mammary artery, the involvement of the cyclooxygenase and the lipoxygenase pathways of arachidonic acid metabolism in the contraction induced by angiotensin II.. Rings of human internal mammary arteries were suspended in organ baths for recording of isometric tension. In addition, the release of eicosanoids in response to angiotensin II (0.3 microM) was measured by enzyme immunoassay.. In human arterial rings without endothelial dependent relaxation in response to substance P or acetylcholine, the angiotensin II-induced contractions were significantly (P<0.05) reduced by 27% in the presence of GR32191 0.3 microM (thromboxane A(2) (TXA(2)) receptor antagonist) but remained unchanged in the presence of dazoxiben 100 microM (thromboxane synthase inhibitor). In addition, angiotensin II failed to modify TXB(2) and 6-keto-PGF(1alpha) production. These results suggest the contribution of a TXA(2)/PGH(2) agonist other than TXA(2) in angiotensin II-induced contractions. However, indomethacin increased (P<0.05) angiotensin II-mediated contractile response and cysteinyl leukotriene production, suggesting a redirection of arachidonic acid metabolism from the cyclooxygenase pathway to the lipoxygenase pathway. Indeed, the contractions induced by angiotensin II were inhibited (P<0.05) by phenidone 100 microM (cyclooxygenase and lipoxygenase inhibitor), baicalein 100 microM (5-, 12- and 15-lipoxygenases inhibitor), AA861 10 microM (5-lipoxygenase inhibitor) and MK571 1 microM (CysLT(1) receptor antagonist). Cysteinyl leukotrienes were released in response to angiotensin II (pg/mg dry weight tissue: 32+/-9 (basal, n=6) vs. 49+/-9 (angiotensin II 0.3 microM, n=6), P<0.05). LTD(4), and at a lesser degree LTC(4), induced contractions of internal mammary artery and MK571 1 microM abolished the contraction to LTD(4).. This study suggests that the in vitro vasoconstrictor effects of angiotensin II in human internal mammary artery are enhanced at least in part by eicosanoids produced by the cyclooxygenase pathway, probably PGH(2), acting on TXA(2)/PGH(2) receptors, and by lipoxygenase-derived products, particularly cysteinyl leukotrienes acting on CysLT(1) receptors.

Topics: 6-Ketoprostaglandin F1 alpha; Acetylcholine; Angiotensin II; Benzoquinones; Biphenyl Compounds; Cyclooxygenase Inhibitors; Depression, Chemical; Dose-Response Relationship, Drug; Enzyme Inhibitors; Flavanones; Flavonoids; Heptanoic Acids; Humans; Imidazoles; In Vitro Techniques; Indomethacin; Leukotrienes; Lipoxygenase Inhibitors; Mammary Arteries; Propionates; Pyrazoles; Quinolines; Receptors, Thromboxane; Substance P; Thromboxane B2; Thromboxane-A Synthase; Vasoconstriction