ABSTRACT
The present study describes the effects of an extract obtained from the leaves of Ligstrum purpurascens and acteoside purified from the extract on the contractile response to various agonists in rat isolated aortic rings. L. purpurascens extract relaxed 9,11-dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha (U46619)-preconstricted rings in a concentration-dependent manner (IC50: 0.14 +/- 0.01 mg/ml with endothelium and 0.16 +/- 0.01 mg/ml without endothelium). The extract also reduced contraction induced by 35 mM K+ or by 1 microM phorbol 12,13-diacetate (PDA) in endothelium-intact rings. The extract (0.1-0.3 mg/ml) reduced the concentration-response to U46619 in normal Krebs solution or to CaCl2 in 35 mM K(+)-containing solution. Acteoside accounts for 2.05% of total L. purpurascens extract in weight. Acteoside induced relaxation of rings preconstricted by U46619 (IC50: 0.22 +/- 0.01 mg/ml) but it caused an increase in 35 mM K(+)-induced tone. Removal of endothelium enhanced the relaxing effect of acteoside. Besides, pretreatment with acteoside inhibited endothelium/nitric oxide-mediated relaxation induced by acetylcholine. These results indicate that acteoside is unlikely the major ingredient responsible for the vasodilator effect of L. purpurascens extract. The extract relaxed the preconstricted aortic rings probably through multiple mechanisms by acting on smooth muscle cells. The inhibitory effect on endothelial nitric oxide-mediated relaxation suggests that acteoside could also act on the endothelial cells to reduce nitric oxide release.
Subject(s)
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/agonists , Aorta, Thoracic/drug effects , Aorta, Thoracic/microbiology , Drugs, Chinese Herbal/chemistry , Glucosides/isolation & purification , Glucosides/pharmacology , Phenols , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Receptors, Thromboxane/agonists , Vasodilator Agents/isolation & purification , Vasodilator Agents/pharmacology , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Acetylcholine/pharmacology , Animals , Dose-Response Relationship, Drug , Endothelium/drug effects , Glucosides/chemistry , Male , Molecular Structure , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Nifedipine/pharmacology , Nitric Oxide/pharmacology , Papaverine/pharmacology , Phenylephrine/pharmacology , Phorbol Esters/pharmacology , Plant Leaves/chemistry , Rats , Rats, Sprague-Dawley , Vasodilator Agents/chemistryABSTRACT
Chemically modified hemoglobins are potential oxygen-carrying blood substitutes, but their in vivo administration has been associated with a variety of unexpected side events, including increased platelet reactivity. We studied the effects of hemoglobin A0 (HbA0) and alpha-crosslinked hemoglobin (alpha-DBBF) on platelets in vitro. Neither hemoglobin A0 nor alpha-DBBF activated platelets when added alone, but both proteins potentiated submaximal agonist-induced platelet aggregation without increasing other markers of platelet activation such as serotonin secretion. Only agonists that are known to cause release of platelet arachidonic acid (AA) were potentiated while aggregation induced by ADP, which does not release AA, was not potentiated. Blockade of the thromboxane receptor with SQ-29,548 prevented the HbA0-induced and the alpha-DBBF-induced potentiation suggesting that the AA/thromboxane signaling pathway mediates the interaction of platelets with hemoglobin.
