Biomedical subjects

Fumitaka Ikomi

Publications and source records attributed to Fumitaka Ikomi.

13 recordsLinked to original sources

PubMed2006

Noradrenaline-induced smooth muscle relaxation in the specific region of canine facial vein: implications for facial and cranial circulation.

This study was performed to investigate the heterogeneity of physiological and pharmacological properties in segments of the facial veins with special reference to selective brain cooling. Canine facial veins were isolated and the isometric tension of each segment was measured using the organ bath technique. Vessels in the segments of the facial veins that run opposite to the buccal cavity automatically produced myogenic tone and tended to show spontaneous contractions, but vessels in other segments did not. When no contractile agent was used for precontraction, noradrenaline and adrenaline produced dose-dependent relaxations in the former venous segments, but contractions in the latter ones. A Schild plot analysis for metoprolol against denopamine and for ICI118,551 against salbutamol showed that the venous segments running opposite the buccal cavity contained both beta(1)- and beta(2)-adrenoceptors, but the other venous segments contained only beta(2)-adrenoceptors. Electrical field stimulation-induced tetrodotoxin-sensitive relaxations in the former venous segments were diminished by pretreatment with metoprolol, but not with ICI118,551, indicating that the electrical stimulation-induced relaxation may be related to the activation of beta(1)-adrenoceptors in the venous smooth muscles. In conclusion, the heterogeneity of the functional properties, especially in the distribution of beta-adrenoceptors, in different segments of canine facial veins was observed in the present study, and autoregulatory mechanisms, humoral mechanisms, and neural mechanisms were suggested to affect cranial venous drainage.

Adrenergic Agonists↗

PubMed2005

Cilostazol, an inhibitor of type 3 phosphodiesterase, produces endothelium-independent vasodilation in pressurized rabbit cerebral penetrating arterioles.

We investigated the effects of cilostazol, a potent inhibitor of cGMP-inhibited cAMP phosphodiesterase, on mechanical activity of isolated pressurized rabbit cerebral penetrating arterioles with special reference to the function of the endothelium. Both cilostazol and milrinone, another inhibitor of cAMP phosphodiesterase, produced vasodilation of the cerebral penetrating arterioles in a dose-dependent manner. Pretreatment with selective inhibitors of cyclooxygenase or nitric oxide synthase, or chemical denudation of the endothelial cells caused no significant effect on the cilostazol-mediated vasodilation of the cerebral arterioles. A selective large-conductance calcium-activated potassium channel inhibitor, iberiotoxin, and a selective protein kinase A inhibitor, H-89, caused no significant effect on the cilostazol-mediated vasodilation. In the cerebral arterioles, low concentration (10(-6)M) of cilostazol or milrinone caused a significant shift of the dose-vasodilatory response curve for adenosine to the left. These findings suggest that cilostazol produces vasodilation independent of the presence of the endothelium or activation of endogenous vasodilative prostaglandins, nitric oxide, calcium-activated potassium channel and protein kinase A. In conclusion, the vasodilator action of cilostazol may, in part, contribute to the beneficial effect of preventing lacunar cerebral infarction in patients with functional damage of the endothelium in cerebral penetrating arterioles.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

A new preparation for visualizing lymphatic flow pathway in isolated rat lymph nodes.

BACKGROUND: There is no reported study in which the lymphatic flow pathway in lymph nodes has been visualized and investigated in in vitro studies. The purpose of the present study is first to develop an isolated rat lymph node preparation circulated through the afferent and efferent lymph vessels in order to visualize lymphatic flow pathway within the node by using a video microscope system, and then to evaluate lymphatic flow dynamics by using fluorescence-labeled substances. METHODS AND RESULTS: In the present study, rat iliac lymph node was isolated. The afferent and efferent lymph vessels of the lymph node were cannulated with glass micropipettes in an organ chamber, while the small-sized arteries and veins connected to the lymph node were secured with sutures. Krebs-bicarbonate solution with or without fluorescent probes [FITCdextran, mol. weight; 77,000 and/or fluoresbrite carboxylate-microspheres (FC-microspheres) mean diameter of 1 microm] was circulated through the lymph vessels of the node. The time-dependent lymphatic pathway of fluorescent probes was investigated with a video microscope system. FTIC-dextran first spread through the cortex and subsequently reached the medulla of the lymph node. A follicle-like structure became evident in the cortex. FITC-dextran appeared in the efferent lymph vessel at 109 +/- 21 sec after its circulation began, while FC-microspheres distributed in the lymph node did not emerge from the node within 20 min after their introduction. CONCLUSIONS: In vitro preparations constructed in the present study will enable us to visualize the lymphatic flow pathway of fluorescent substances within the isolated iliac lymph nodes of rats in the absence of blood circulation.

Animals↗

PubMed2004

Current topics of physiology and pharmacology in the lymphatic system.

We have reviewed physiological significance of rhythmical spontaneous contractions of collecting lymph vessels, which play a pivotal role in lymph transport and seem to control lymph formation through changing the pacemaker sites of the rhythmic contractions and contractile patterns of the lymphangions. A characteristic feature that the rhythmic pump activity works in vivo physiologically under the specific environment of lower oxygen tension in lymph (25-40 mm Hg) has been evaluated. With the characteristic feature, generation of endogenous nitric oxide (NO) from lymphatic endothelial cells and/or activation of ATP-sensitive potassium channels (K(ATP)) are reviewed to play crucial roles in the regulation of lymph transport at physiological or pathophysiological conditions. Chemical substances released from malignant tumor cells and tumor-derived parathyroid hormone-related peptide (PTHr-P) are also shown to cause a significant reduction of lymphatic pump activity through generation of endogenous NO and activation of K(ATP) channels. Finally, we have discussed physiological significance and roles of the lower oxygen tension in lymph, generation of endogenous NO, and activation of K(ATP) in lymph formation, lymph transport, and the functions of lymph nodes.

Adenosine Triphosphate↗

PubMed2004

ATP inhibits pump activity of lymph vessels via adenosine A1 receptor-mediated involvement of NO- and ATP-sensitive K+ channels.

We examined the effects of ATP on intrinsic pump activity in lymph vessels isolated from the rat. ATP caused significant dilation with a cessation of lymphatic pump activity. Removal of the endothelium or pretreatment with Nomega-nitro-L-arginine methyl ester (L-NAME) significantly reduced ATP-induced inhibitory responses of lymphatic pump activity, whereas reduction was not suppressed completely by 10(-6) M ATP. L-arginine significantly restored ATP-induced inhibitory responses in the presence of L-NAME. ATP-induced inhibitory responses in lymph vessels with endothelium were also significantly, but not completely, suppressed by pretreatment with glibenclamide. 8-Cyclopentyl-1,3-dipropylxanthine (a selective adenosine A1 receptor antagonist), but not suramine (a P2X and P2Y receptor antagonist) or 3,7-dimethyl-1-proparglyxanthine (a selective adenosine A2 receptor antagonist), significantly decreased ATP-induced inhibitory responses. alpha,beta-methylene ATP (a selective P2X and P2Y receptor agonist) had no significant effect on lymphatic pump activity. In some lymph vessels with endothelium (24 of 30 preparations), adenosine also caused dose-dependent dilation with a cessation of lymphatic pump activity. L-NAME significantly reduced the inhibitory responses induced by the lower (3 x 10(-8)-3 x 10(-7) M) concentrations of adenosine. Glibenclamide or 8-cyclopentyl-1,3-dipropylxanthine also significantly suppressed adenosine-induced inhibitory responses. These findings suggest that ATP-induced dilation and inhibition of pump activity of isolated rat lymph vessels are endothelium-dependent and -independent responses. ATP-mediated inhibitory responses may be, in part, related to production of endogenous nitric oxide, involvement of ATP-sensitive K+ channels, or activation of adenosine A1 receptors in lymphatic smooth muscle and endothelium.

Adenosine Triphosphate↗

PubMed2004

PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis.

Cancer metastases are commonly found in the lymphatic system. Like tumor blood angiogenesis, stimulation of tumor lymphangiogenesis may require the interplay of several tumor-derived growth factors. Here we report that members of the PDGF family act as lymphangiogenic factors. In vitro, PDGF-BB stimulated MAP kinase activity and cell motility of isolated lymphatic endothelial cells. In vivo, PDGF-BB potently induced growth of lymphatic vessels. Expression of PDGF-BB in murine fibrosarcoma cells induced tumor lymphangiogenesis, leading to enhanced metastasis in lymph nodes. These data demonstrate that PDGF-BB is an important growth factor contributing to lymphatic metastasis. Thus, blockage of PDGF-induced lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic metastasis.

Animals↗

PubMed2003

Establishment of rat lymphatic endothelial cell line.

OBJECTIVE: The objective of the present study was to establish a rat lymphatic endothelial cell line and then to investigate the morphological and immunohistochemical properties of the cells. METHODS: The lymphatic endothelial cells of rat thoracic ducts were isolated enzymatically by trypsin digestion and were cultured in endothelium growth medium (EGM)-2 in an atmosphere of low oxygen (5% O(2), 5% CO(2), and 90% N(2)) or high oxygen (21% O(2), 5% CO(2), and 74% N(2)). RESULTS: The number of the cells cultured in the low-oxygen atmosphere was significantly larger than that obtained in the high-oxygen atmosphere. The cultured cells in the low-oxygen atmosphere showed a monolayer with uniform cobblestone appearance, suggesting the morphological properties of endothelial cells. Factor VIII-related antigen and cell surface carbohydrates (i.e., D-galactose alpha and D-N-acetylgalactosamine alpha) were found on the lymphatic cultured cells. The phagocytosis of 1,1-diocadecyl1-3,3,3',3'-tetramethylindo-carbocyanine perchlorate-labeled acetylated low-density lipoprotein also was observed in the cultured cells. The cytoskeleton protein F-actin was located on the plasma membrane of the cultured cells as circumferential thin bundles and in the cytoplasma as filamentous bundles. CONCLUSIONS: The present study indicates that the choice of EGM-2 as a culture medium and the hypoxic atmosphere ( approximately 5%) enabled us to establish rat lymphatic endothelial cell line.

Actins↗

PubMed2003

Flow-mediated release of nitric oxide from lymphatic endothelial cells of pressurized canine thoracic duct.

We examined the effects of flow on lymphatic endothelial cells by using conventional cascade preparations of isolated coronary arteries without intact endothelium. The pressurized thoracic ducts were intraluminally perfused at a constant flow rate ranging from 0.5 to 2.0 ml/min. A linear relationship was observed between the flow rate and the normalized amount of relaxing substance(s) released from the lymphatic endothelial cells. Thus the flow rate of 2.0 ml/min produced approximately 39% of sodium nitroprusside (SNP)-produced maximal relaxation in the cascade arterial rings. The acetylcholine (ACh, 10(-5) M)- and flow-induced relaxations of the cascade arterial rings were completely reduced by the mechanical rubbing of lymphatic endothelial cells in the pressurized lymph vessels. Pretreatment with 5 x 10(-5) M N(G)-nitro-L-arginine methyl ester (L-NAME) on the lymphatic endothelial cells caused a significant reduction of the ACh- and flow-induced vasodilations of the cascade arterial rings. Pretreatment with 10(-5) M indomethacin on the lymphatic endothelial cells produced no significant effect on the ACh- and flow-induced vasodilations. These findings suggest that lymphatic endothelial cells of canine thoracic ducts can produce and release endogenous nitric oxide by stimulation of flow (approximately 2.0 ml/min).

Acetylcholine↗

PubMed2003

Estrogen-induced augmentation of endothelium-dependent nitric oxide-mediated vasodilation in isolated rat cerebral small arteries.

We examined chronic effects of 17beta-estradiol (E(2)beta) on the responses of isolated rat anterior cerebral small arteries to vasoactive substances with special reference to endothelial function. Female Sprague-Dawley rats were separated into four groups: (1) sham-operated group (Sham), (2) sham-operated plus E(2)beta treated group (Sham+E), (3) ovariectomized group (OVX), (4) ovariectomized plus E(2)beta treated group (OVX+E). 5-Hydroxytryptamine (5-HT) (10(-10)-10(-3) M) and U46619 (10(-15)-10(-8) M) induced concentration-dependent contractions in the cerebral small arteries. The 5-HT- and U46619-induced contractions were not affected by pretreatment with 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME). No significant difference in high potassium (80 mM)- and the agonists-mediated contractions was observed among the four groups. Administration of acetylcholine (ACh) (10(-9)-10(-3) M) and sodium nitroprusside (SNP) (10(-8)-10(-3) M) caused dose-related relaxations in the cerebral small arteries precontracted by 10(-8) M U46619. Chronic treatment with E(2)beta caused a significant potentiation of the ACh-induced relaxations in the Sham+E and OVX+E groups. The dose-response curve for ACh in the OVX group was quite similar to that obtained with the Sham group. The ACh-induced relaxation was reduced significantly by pretreatment with 3 x 10(-5) M L-NAME, and an additional treatment with 10(-3) M L-arginine reversed significantly the L-NAME-induced inhibition. The removal of endothelial cells produced a significant reduction of the ACh-induced relaxation. Indomethacin (10(-5) M) did not alter the ACh-induced relaxation. The findings suggest that E(2)beta potentiates ACh-induced endothelium-dependent relaxation in rat anterior cerebral arteries and that the potentiation may be, in part, mediated by increasing production and release of endogenous NO from the endothelial cells.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2002

Electrical stimulation-induced alpha1- and alpha2-adrenoceptors-mediated contractions of isolated canine lymph nodes.

The contractile effects of alpha-adrenoceptor agonists and field electrical stimulation were investigated pharmacologically in canine isolated tracheobronchial lymph nodes. Addition of noradrenaline (NA), phenylephrine (Phe) and UK14,304 caused dose-related contractions of the isolated lymph nodes. Pretreatment with prazosin (3 x 10(-9), 3 x 10(-8) and 3 x 10(-7) M) shifted the concentration-response curve for phenylephrine to the right, whereas yohimbine (3 x 10(-7) M) did not affect the contractile responses to phenylephrine. On the other hand, the concentration-response curve for UK 14,304 shifted to the right by treatment with yohimbine (3 x 10(-9), 3 x 10(-8) and 3 x 10(-7) M) but not by prazosin (3 x 10(-7) M). Field electrical stimulation (25 V, 0.7 ms, 16 Hz) produced contractile responses of the lymph nodes. The electrical stimulation-induced contractions were completely reduced by pretreatment with tetrodotoxin (TTX) (3 x 10(-7) M) or bretylium (10(-6) M). Furthermore, phentolamine (10(-8), 10(-7) and 10(-6) M), prazosin (3 x 10(-9) and 3 x 10(-8) M) and yohimbine (3 x 10(-8) and 3 x 10(-7) M) significantly reduced the electrical stimulation-induced contractions in the preparations. The present findings suggest that there are both alpha1- and alpha2-adrenoceptors located on the smooth muscle cells in canine tracheobronchial lymph nodes, and that the adrenoceptors-mediated excitatory mechanisms of adrenergic innervation exist in the lymph nodes.

Adrenergic alpha-Agonists↗

PubMed2002

Development of pressurized retinal resistance-sized arteriolar preparation with special reference to acetylcholine-induced nitric-oxide-mediated vasodilatation.

We examined the responses of pressurized bovine retinal functional arterioles (97-185 microm in diameter and approximately 3 mm long) to vasoactive substances and the mode of action of acetylcholine (ACh) on the pressurized arterioles. The retinal arterioles were cannulated at both ends with glass micropipettes and perfused at a constant pressure of 60 mmHg. Vasoconstrictions of the retinal arterioles were induced by prostaglandin F(2 alpha) (PG F(2 alpha)), U46,619, noradrenaline (NA), and 5-hydroxytryptamine (5-HT) in a dose-dependent manner. The decreasing order of potency (pD(2) value) in the constrictive responses was as follows: 5-HT = U46,619 > NA > PG F(2 alpha). On the other hand, sodium nitroprusside (SNP), isocarbacyclin (a stable prostaglandin I(2) analog), ACh, and isoproterenol (ISP) caused dose-dependent vasodilatation in the pressurized retinal arterioles preconstricted with high-potassium solution (40 mM K+). The decreasing order of potency in the vasodilative responses was as follows: isocarbacyclin > SNP > ACh. The ACh-induced vasodilatation was suppressed significantly by pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME) (3 x 10(-5) M). A treatment with L-arginine (10(-3) M) in the presence of 3 x 10(-5) M L-NAME reversed completely the L-NAME-induced reduction of the vasodilatation. These results suggest that ACh causes the production and release of endogenous nitric oxide or its related compounds, which results in vasodilatation of the pressurized bovine retinal functional arterioles.

Acetylcholine↗

PubMed2002

Plasma-mediated potentiation in prostanoid-induced contractions in isolated canine external jugular veins.

We examined the effects of plasma on contractile responses of isolated dog external jugular veins to a thromboxane A(2) analog, U46619, and noradrenaline. Pretreatment with 1.0% plasma in Krebs-bicarbonate solution, but not 0.1%, caused a significant left and upward shift in the concentration-contractile response curve for U46619. The plasma-mediated potentiation of the response to U46619 was found in the venous segments without intact endothelium. The administration of 2x10(-5) M lysophosphatidylcholine in Krebs-bicarbonate solution with no plasma also produced a significant left and upward shift of the concentration-contractile response curve for U46619, the shift being quite similar to that obtained with 1.0% plasma. In contrast, pretreatment with 1.0% plasma or 2x10(-5) M lysophosphatidylcholine produced no significant effect on the noradrenaline-mediated contractions in the venous segments. Pretreatment with 10(-4) M L-ascorbate or 0.1 mg/ml alpha-tocopherol in the presence of 1.0% plasma caused a significant reduction in the plasma-mediated potentiation of the contractile responses to U46619. These findings suggest that lysophosphatidylcholine, a major phospholipid component of oxidized low-density lipoproteins, may contribute, in part, to the plasma-mediated potentiation of contractile responses of the isolated veins to U46619, and that the antioxidant vitamin, L-ascorbate, or alpha-tocopherol significantly reduces the plasma-mediated potentiation of the contractile responses to U46619, which may be related to inhibiting the production of lysophosphatidylcholine in plasma.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMedDate not supplied

Recanalization of the collecting lymphatics in rabbit hind leg.

OBJECTIVE: This study was designed to examine whether mature collecting lymphatics can regenerate in the adult tissue or not. MATERIALS AND METHODS: The X-ray lymphograms were used to detect network of the collecting lymphatics in rabbit hind leg. Regeneration of the lymphatics was observed after surgical removal of the popliteal lymph node or a part of the popliteal afferent lymphatic. Structure and mechanical properties of the lymphatics were also examined by light and electron microscopes and in vitro functional experiments. RESULTS: One week after removal of the lymph node, only an afferent lymphatic and a deposit of the contrast medium at the popliteal region were observed. Four weeks after the removal, the connection of the afferent and efferent lymphatics at the popliteal region, and collateral lymphatics were present in the leg. Further, 4 weeks after 1-mm excisions of a part of the lymphatic, recanalization was observed between the central and peripheral cut ends of the lymphatic but not after 3- and 10-mm excisions. Endothelial cells and smooth muscle cells could be observed by electron microscope, and contractile proteins, and alpha-smooth muscle actin SM1 and SM2 were immunofluorescently detected in both intact and the regenerated lymphatic walls. In both lymphatics, norepinephrine and acetylcholine induced dose-dependent constriction and dilation of the vessels, respectively. CONCLUSION: The present study demonstrated that mature collecting lymphatics are able to regenerate in the adult tissues.

Animals↗