Biomedical subjects
Publications and source records attributed to F Sekiguchi.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
1. The influence of the passive force on the contraction and endothelium-dependent relaxation in aortae of normotensive Wistar Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) were compared. 2. Force changes of endothelium-intact and -removed preparations were measured isometrically by a force-displacement transducer. Endothelium-dependent relaxation was observed by applying acetylcholine to the preparation precontracted in the presence of 5 x 10(-7) mol/L noradrenaline. 3. The preparations showed spontaneously developed tension (tone) that increased with the increase in the passive force. The effect of passive force was greater in preparations from SHRSP. Contraction initiated by noradrenaline was also increased by passive force up to 30 mN, then showed a tendency to decrease. 4. Endothelium-dependent relaxation was depressed as the passive force was increased. Preparations from SHRSP showed impaired endothelium-dependent relaxation and were influenced by passive force to a lesser degree when compared with preparations from WKY rats. 5. Relaxation by sodium nitroprusside was influenced by passive force to a much lesser extent than that by acetylcholine. 6. Indomethacin potentiated endothelium-dependent relaxation and blocked the effect of passive force in both preparations. 7. The difference in relaxation and the effect of passive force is primarily caused by the difference in the release of endothelium-derived contracting factor, which is thought to be a product of the cyclo-oxygenase pathway of the arachidonic acid cascade.
Influences of endothelium on contraction of aortic smooth muscle by various agents were studied and those in the preparations from Wistar Kyoto rat (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were compared. Endothelium depressed the contractions induced by noradrenaline and 5-hydroxytryptamine (5-HT). The time course of the contraction was bi- or tri-phasic in the former and slow rising monophasic in the latter. On the other hand, the depression was weaker in the contraction by prostaglandin F2alpha- and high K+. The depression was blocked by the removal of endothelium or in the presence of Nomega-nitro-L-arginine (L-NNA), indicating that nitric oxide (NO) released from endothelium was responsible for the inhibition. The inhibition was weaker in the preparation from SHRSP when compared to that in the preparation from WKY. Relaxation by acetylcholine (ACh) of the preparation precontracted in the presence of respective contractile agent was impaired in the preparation from SHRSP. It is concluded that mode of inhibition of the contraction varies depending on the agents used to initiate the contraction, i.e. depending on the mode of the release of NO. In the preparation from SHRSP, the influence of endothelium is impaired due to the reduced release of NO.
Control of the active tone by endothelium in aortae from various strains of spontaneously hypertensive rats was studied. The active tone was negligibly observed in endothelium-intact preparation. The application of N(G)-nitro-L-arginine (L-NNA, 10(-4) M) induced slowly developed active tone in the preparations from hypertensive rats but no active tone was induced in the preparation from normotensive Wistar Kyoto rats (WKY). The developed tension was stronger in preparations from rats with higher blood pressure as observed in endothelium denuded preparations. The developed active tone in the presence of L-NNA was greater than that observed in endothelium denuded preparations. The active tone was abolished by the removal of extracellular Ca2+ or by the application of Ca-antagonists. L-arginine counteracted the effects of L-NNA and depressed the developed active tone in the presence of the latter drug. The application of indomethacin (10(-5) M) depressed the active tone of the preparations from SHRSP by 25.5+/-5.2%. Increasing extracellular K+ concentration or application of tetraethylammonium (TEA) could not be used to observe the effect of endothelium-derived factors on the active tone, because of their strong contractile effect. Simultaneous application of apamin and charybdotoxin induced an elevation of tension which was often associated with spontaneous tension oscillation. It is concluded that the active tone, which is smooth muscle origin, is depressed by endothelium-derived nitric oxide (NO) strongly and potentiated by a product of arachidonic acid cascade through cyclooxygenase pathway. The involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressing effect of endothelium is thought to be small.
The effect of tranexamic acid on the growth of three human tumor cell lines (lung squamous cell carcinoma QG-56, lung adenocarcinoma PC-12 and ovarian carcinoma OC-1) was investigated in vitro and in vivo in nude mice. Tranexamic acid exhibited no direct cytotoxicity in vitro, but it inhibited the growth of all the three cell lines as tumors in nude mice. Prominent deposition of fibrin or fibrinogen around tumor cells at the advancing border were observed only in the tumors of treated animals.