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Kazumasa Shinozuka - One of the best experts on this subject based on the ideXlab platform.

  • Effects of nicorandil on sympathetic neurotransmission in rat Caudal Artery.
    Clinical and experimental pharmacology & physiology, 2010
    Co-Authors: Ami Tei, Satomi Kagota, Namie Nejime, Yukari Tada, Yoko Tanabe, Michio Hashimoto, Kazumasa Shinozuka
    Abstract:

    1. We examined the effects of nicorandil, an ATP-sensitive potassium (K(ATP)) channel opener and nitric oxide donor, on the release of noradrenaline from vascular sympathetic nerves. This effect was compared to the effect on vascular smooth muscle. 2. Caudal Artery preparations from Wistar rats were electrically stimulated (1 Hz, 0.5-ms duration) and noradrenaline release in the Artery was detected using an high-pressure liquid chromatography-electrochemical detection technique. The pharmacological properties of the prejunctional effect of nicorandil were determined using the nonselective K(ATP) channel blocker glibenclamide, the pancreatic beta-cell and brain-type K(ATP) channel blocker tolbutamide, and the smooth muscle-type K(ATP) channel blocker PNU-37883A. 3. Nicorandil inhibited the electrical stimulation-evoked noradrenaline release in a concentration-dependent manner. This inhibitory effect was abolished by 1 micromol/L glibenclamide and 10 micromol/L tolbutamide, but was not affected by 10 micromol/L PNU-37883A or 0.3 micromol/L ODQ. Nicorandil did not affect the noradrenaline transporter uptake 1 in the adrenergic nerve terminals. 4. Nicorandil produced a relaxation response in a concentration-dependent manner in the Caudal Artery pre-contracted with 0.3 micromol/L noradrenaline. This relaxation response was significantly diminished in the presence of 1 micromol/L glibenclamide, 10 micromol/L PNU-37883A and 0.3 micromol/L ODQ but not by 10 micromol/L tolbutamide. 5. These findings suggest that nicorandil inhibits noradrenaline release via the K(ATP) channels of sympathetic nerves. These channels may be pharmacologically different from those of vascular smooth muscle.

  • Nicorandil-induced ATP release in endothelial cells of rat Caudal Artery is associated with increase in intracellular Ca2+
    European journal of pharmacology, 2001
    Co-Authors: Michio Hashimoto, Kazumasa Shinozuka, Tetsuya Sasaki, Naoko Tanaka, Shahdat Hossain, Yoko Kubota, Katsuhiro Tamura, Osamu Shido, Masaru Kunitomo
    Abstract:

    The effect of nicorandil, an ATP-sensitive K(+) channel opener, on the level of intracellular Ca(2+) ([Ca(2+)](i)) and on ATP release in endothelial cells of the rat Caudal Artery was examined using a fluorescent confocal microscopic imaging system and high-performance liquid chromatography (HPLC) with fluorescent detection, respectively. Nicorandil significantly increased [Ca(2+)](i) and the overflow of ATP and its metabolites. The former reaction was abolished in the absence of extracellular Ca(2+), but it did not change in the presence of thapsigargin or cyclopiazonic acid. The increase in the overflow of ATP and [Ca(2+)](i) induced by nicorandil was markedly suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. The increase of [Ca(2+)](i) induced by nicorandil was significantly and inversely correlated with the level of intracellular ATP in the endothelial cells, suggesting that activation of ATP-sensitive K(+) channels by nicorandil increases Ca(2+) influx in endothelial cells. The increase of [Ca(2+)](i) might be associated with ATP release.

  • Both extracellular ATP and shear stress regulate the release of nitric oxide in rat Caudal Artery.
    Clinical and experimental pharmacology & physiology, 1999
    Co-Authors: Young Mi Kwon, Kazumasa Shinozuka, Satomi Kagota, Yu Yamaguchi, Kazuki Nakamura, Masaru Kunitomo
    Abstract:

    1. To elucidate the physiological role of nitric oxide (NO) in regulating vascular tone, the effects of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, on the vasoconstrictor response to noradrenaline (NA) in rat Caudal Artery was examined. 2. NG-Nitro-L-arginine methyl ester significantly potentiated the NA-induced increase in perfusion pressure in the perfused Caudal Artery, but did not affect the NA-induced contraction in Caudal Artery ring preparations. In addition, an increase in perfusion pressure mechanically produced by a stepwise increase in flow rate was not affected by L-NAME. 3. Noradrenaline evoked a significant increase in the release of endogenous ATP and its metabolites from the perfused Artery, whereas increased perfusion pressure as a result of increased flow rate did not evoke release of endogenous ATP. 4. In the presence of exogenously applied ATP, L-NAME significantly potentiated the increase in perfusion pressure produced by increased flow rate. 5. These results indicate that perfused vascular tone is regulated by endogenous NO and suggest that extracellular ATP may participate in the synthesis and release of NO by shear stress in endothelial cells in the rat Caudal Artery.

  • Determination of ATP and Its Metabolites Released from Rat Caudal Artery by Isocratic Ion-Pair Reversed-Phase High-Performance Liquid Chromatography
    Analytical biochemistry, 1998
    Co-Authors: Yoko Kawamoto, Kazumasa Shinozuka, Masaru Kunitomo, Jun Haginaka
    Abstract:

    A sensitive and selective assay method for adenine compounds (purines) using high-performance liquid chromatography with fluorescent detection was developed. The 1,N6-ethenoderivatives of adenine, adenosine, AMP, ADP, and ATP formed by reaction with chloroacetaldehyde at 80 degreesC were separated by ion-pair reversed-phase chromatography within 15 min under isocratic conditions. alpha,beta-Methylene adenosine 5'-diphosphate could be used as an internal standard for the determination of purines. The calibration graphs constructed with peak area ratios against amounts were linear between 0.1 and 10.0 pmol of each purine. The repeatability and intermediate precision were less than 6% (RSD, n = 5) and 8% (RSD, n = 3), respectively, at 0.5 pmol of each purine. A method for calculation of each purine amount which considers hydrolysis by derivatization is described. The optimized method was applied to determine the purines released from the rat Caudal Artery stimulated by noradrenaline.

  • Long-term supplementation with a high cholesterol diet decreases the release of ATP from the Caudal Artery in aged rats
    Life sciences, 1998
    Co-Authors: Michio Hashimoto, Young Mi Kwon, Kazumasa Shinozuka, Masaru Kunitomo, Yoko Tanabe, Hossain Md Shahdat, Shuji Gamoh, Yasuakira Tanaka, Sumio Masumura
    Abstract:

    We examined the effects of high cholesterol (HC) diet on the spontaneous and noradrenaline-induced release of ATP, ADP, AMP and adenosine from Caudal arteries and on the plasma levels of these adenyl purines in aged (100-week-old) Wistar rats. Administration of this diet for 12 weeks significantly reduced spontaneous and noradrenaline (1 micromol/L)-evoked release of adenyl purines from the Caudal arteries relative to rats given the control diet The unsaturation index of fatty acids (UI), which gives the average number of double bonds, of both the plasma and the Caudal Artery was significantly less in the HC diet-fed rats than in those fed the control diet. The HC diet for 12 weeks produced a slight but significant increase in systolic and diastolic blood pressure with advancing age. Regression analysis revealed a significant inverse relationship between the total amount of purines released from the Artery and diastolic blood pressure, and also a positive relationship between the total amount of purines released and the UI of the Caudal Artery. These results suggest that the high cholesterol diet decreased the release of adenyl purines from the Caudal arteries of aged rats, leading to an increase in blood pressure.

Sue P. Duckles - One of the best experts on this subject based on the ideXlab platform.

  • MT(2) melatonin receptors are present and functional in rat Caudal Artery.
    The Journal of pharmacology and experimental therapeutics, 2002
    Co-Authors: Monica I. Masana, Sue P. Duckles, Suzanne Doolen, Cagatay Ersahin, Walid M. Al-ghoul, Margarita L. Dubocovich, Diana N. Krause
    Abstract:

    In rat Caudal Artery, contraction to melatonin results primarily from activation of MT1 melatonin receptors; however, the role of MT2 melatonin receptors in vascular responses is controversial. We examined and compared the expression and function of MT2 receptors with that of MT1 receptors in male rat Caudal Artery. MT1 and MT2 melatonin receptor mRNA was amplified by reverse transcription-polymerase chain reaction from Caudal arteries of three rat strains (i.e., Fisher, Sprague-Dawley, and Wistar). Antisense (but not sense)33P-labeled oligonucleotide probes specific for MT1 or MT2 receptor mRNA hybridized to smooth muscle, as well as intimal and adventitial layers, of Caudal Artery. In male Fisher rat Caudal Artery denuded of endothelium, melatonin was 10 times more potent than 6-chloromelatonin to potentiate contraction to phenylephrine, suggesting activation of smooth muscle MT1melatonin receptors. The MT1/MT2 competitive melatonin receptor antagonist luzindole (3 μM), blocked melatonin-mediated contraction (0.1–100 nM) with an affinity constant ( K B value of 157 nM) similar to that for the human MT1 receptor. However, at melatonin concentrations above 100 nM, luzindole potentiated the contractile response, suggesting blockade of MT2 receptors mediating vasorelaxation and/or an inverse agonist effect at MT1constitutively active receptors. The involvement of MT2receptors in vasorelaxation is supported by the finding that the competitive antagonists 4-phenyl 2-acetamidotetraline and 4-phenyl-2-propionamidotetraline, at MT2-selective concentrations (10 nM), significantly enhanced contractile responses to all melatonin concentrations tested (0.1 nM–10 μM). We conclude that MT2 melatonin receptors expressed in vascular smooth muscle mediate vasodilation in contrast to vascular MT1 receptors mediating vasoconstriction.

  • Estradiol modulates vascular response to melatonin in rat Caudal Artery
    American Journal of Physiology-Heart and Circulatory Physiology, 1999
    Co-Authors: Suzanne Doolen, Diana N. Krause, Sue P. Duckles
    Abstract:

    The purpose of this study was to determine whether estrogen modulates the function of vascular melatonin receptors. We used the rat Caudal Artery and found that the contractile effects of melatonin...

  • Melatonin receptors mediate potentiation of contractile responses to adrenergic nerve stimulation in rat Caudal Artery
    European journal of pharmacology, 1995
    Co-Authors: Diana N. Krause, Victor E. Barrios, Sue P. Duckles
    Abstract:

    Abstract The hormone melatonin potentiated contractile responses to adrenergic nerve stimulation in isolated ring segments of rat Caudal Artery. This effect was inhibited by the melatonin receptor antagonist luzindole but not by the serotonin 5-HT 2 receptor antagonist ketanserin. Melatonin had no direct effects on vascular tone. Melatonin agonists potentiated contractile responses with a relative order of potency (2-iodomelatonin, EC 50 = 0.6 nM; melatonin, EC 50 = 4.7 nM; N -acetylserotonin, EC 50 = 1.5 μM) that is consistent with the melatonin ML 1 receptor subtype. Melatonin also potentiated contractions elicited by exogenous norepinephrine and produced its effects in the absence of an intact endothelium. These data suggest that melatonin acts on receptors in the smooth muscle. The Caudal Artery provides a useful functional assay for pharmacological analysis of melatonin receptors. Physiologically, melatonin may activate its receptors at night to influence thermoregulation in the rat by enhancing the effects of sympathetic input to the Caudal Artery.

  • Reserpine-induced supersensitivity in rat Caudal Artery: influence of age.
    Journal of Pharmacology and Experimental Therapeutics, 1991
    Co-Authors: Sue P. Duckles
    Abstract:

    Vascular smooth muscle function does not necessarily deteriorate with advancing age. However, although base-line function may be well maintained, the ability to adapt to stress may decline. Therefore we tested the hypothesis that development of denervation supersensitivity may be impaired in older animals. Fischer-344 rats (6, 12, 20, 24 and 27 months old) were treated with reserpine 0.3 or 0.4 mg/kg i.p. for 7 days, a dose which was sufficient to deplete fully vascular norepinephrine content. Isometric contractile responses to phenylephrine and serotonin of isolated tail Artery rings were determined. In the oldest animals studied, 27 months, chronic reserpine treatment resulted in depressed tail Artery contractile responses, perhaps due to a toxic effect of the reserpine treatment. Reserpine-induced supersensitivity, reflected by a decreased EC50, developed to both agonists at all other ages studied. For serotonin, the degree of reserpine-induced supersensitivity did not change with age. However, for phenylephrine, the shift in the concentration-response curve after reserpine treatment was less in 6-month-old rats as compared to all other ages. There was no change in the development of supersensitivity from 12 to 24 months of age. These findings suggest that the development of reserpine-induced supersensitivity is not impaired in blood vessels of older animals and that the ability to adapt to changing conditions is also maintained with age.

Sergio Bova - One of the best experts on this subject based on the ideXlab platform.

  • Image_1_The Selective Rat Toxicant Norbormide Blocks KATP Channels in Smooth Muscle Cells But Not in Insulin-Secreting Cells.pdf
    2019
    Co-Authors: Simona Saponara, Fabio Fusi, Ottavia Spiga, Alfonso Trezza, Brian Hopkins, Margaret A. Brimble, David Rennison, Sergio Bova
    Abstract:

    Norbormide is a toxicant selective for rats to which it induces a widespread vasoconstriction. In a recent paper, we hypothesized a role of ATP-sensitive potassium (KATP) channels in norbormide-induced vasoconstriction. The current study was undertaken to verify this hypothesis by comparing the effects of norbormide with those of glibenclamide, a known KATP channel blocker. The whole-cell patch-clamp method was used to record KATP currents in myocytes freshly isolated from the rat and mouse Caudal Artery and from the rat gastric fundus, as well as in insulin-secreting pancreatic beta cells (INS-1 cells). Smooth muscle contractile function was assessed on either rat Caudal Artery rings or gastric fundus strips. Molecular modeling and docking simulation to KATP channel proteins were investigated in silico. Both norbormide (a racemic mixture of endo and exo isomers) and glibenclamide inhibited KATP currents in rat and mouse Caudal Artery myocytes, as well as in gastric fundus smooth muscle cells. In rat INS-1 cells, only glibenclamide blocked KATP channels, whereas norbormide was ineffective. The inhibitory effect of norbormide in rat Caudal Artery myocytes was not stereo-specific as both the endo isomers (active as vasoconstrictor) and the exo isomers (inactive as vasoconstrictor) had similar inhibitory activity. In rat Caudal Artery rings, norbormide-induced contraction was partially reverted by the KATP channel opener pinacidil. Computational approaches indicated the SUR subunit of KATP channels as the binding site for norbormide. KATP channel inhibition may play a role in norbormide-induced vasoconstriction, but does not explain the species selectivity, tissue selectivity, and stereoselectivity of its constricting activity. The lack of effect in INS-1 cells suggests a potential selectivity of norbormide for smooth muscle KATP channels.

  • Ca2+ entry blocking and contractility promoting actions of norbormide in single rat Caudal Artery myocytes
    British journal of pharmacology, 2002
    Co-Authors: Fabio Fusi, Gabriella Cargnelli, Simona Saponara, Giampietro Sgaragli, Sergio Bova
    Abstract:

    Aim of the present study was to investigate the effects of norbormide, a selective vasoconstrictor agent of the rat peripheral vessels, on the whole-cell voltage-dependent L-type Ca2+ current (ICa(L)) of freshly isolated smooth muscle cells from the rat Caudal Artery, using either the conventional or the amphotericin B-perforated whole-cell patch-clamp method. Norbormide decreased L-type Ca2+ current in a concentration- and voltage-dependent manner, without modifying the threshold and the maximum of the current-voltage relationship. Norbormide-induced ICa(L) inhibition was reversible upon wash-out. Norbormide both shifted the voltage dependence of the steady-state inactivation curve to more negative potentials by about 16 mV, without affecting the activation curve, and decreased the slope of inactivation. Norbormide, however, did not modify both the activation and the inactivation kinetics of the ICa(L). Norbormide decreased ICa(L) progressively during repetitive step depolarizations, with inhibition depending on the stimulation frequency (use-dependent block) as well as on the holding potential. Addition of 50 μM norbormide caused the contraction of all freshly isolated cells and also of those impaled with the perforated method, but not of those impaled with the conventional method (i.e. dialysed). In conclusion, these results prove norbormide to be a vascular L-type Ca2+ channel inhibitor, which preferentially acts on the inactivated and/or open state of the channel. In rat Caudal Artery smooth muscle, however, this mechanism does not result in a vasodilating effect since it is overwhelmed by the mechanism underlying norbormide-induced vasoconstriction. British Journal of Pharmacology (2002) 137, 323–328. doi:10.1038/sj.bjp.0704877

  • Vasorelaxant properties of norbormide, a selective vasoconstrictor agent for the rat microvasculature.
    British journal of pharmacology, 1996
    Co-Authors: Sergio Bova, Lucia Trevisi, Patrizia Debetto, Lorenzo Cima, Maurizio Fumari, Sisto Luciani, Roberto Padrini, Gabriella Cargnelli
    Abstract:

    Abstract 1. The effects of norbormide on the contractility of endothelium-deprived rat, guinea-pig, mouse, and human Artery rings, and of freshly isolated smooth muscle cells of rat Caudal Artery were investigated. In addition, the effect of norbormide on intracellular calcium levels of A7r5 cells was evaluated. 2. In resting rat mesenteric, renal, and Caudal arteries, norbormide (0.5-50 microM) induced a concentration-dependent contractile effect. In rat Caudal Artery, the contraction was very slowly reversible on washing, completely abolished in the absence of extracellular calcium, and antagonized by high concentrations (10-800 microM) of verapamil. The norbormide effect persisted upon removal of either extracellular Na+ or K+. The contractile effect of norbormide was observed also in single, freshly isolated smooth muscle cells from rat Caudal Artery. 3. In resting rat and guinea-pig aortae, guinea-pig mesenteric Artery, mouse Caudal Artery, and human subcutaneous resistance arteries, norbormide did not induce contraction. When these vessels were contracted by 80 mM KCl, norbormide (10-100 microM) caused relaxation. Norbormide inhibited the response to Ca2+ of rat aorta incubated in 80 mM KCl/Ca2(+)-free medium. Norbormide (up to 100 microM) was ineffective in phenylephrine-contracted guinea-pig and rat aorta. 4. In A7r5 cells, a cell line from rat aorta, norbormide prevented high K(+)- but not 5-hydroxytryptamine-induced intracellular calcium transients. 5. These findings indicate that in vitro, norbormide induces a myogenic contraction, selective for the rat small vessels, by promoting calcium entry in smooth muscle cells, presumably through calcium channels. In rat aorta and arteries from other mammals, norbormide behaves like a calcium channel entry blocker.

Masaru Kunitomo - One of the best experts on this subject based on the ideXlab platform.

  • Nicorandil-induced ATP release in endothelial cells of rat Caudal Artery is associated with increase in intracellular Ca2+
    European journal of pharmacology, 2001
    Co-Authors: Michio Hashimoto, Kazumasa Shinozuka, Tetsuya Sasaki, Naoko Tanaka, Shahdat Hossain, Yoko Kubota, Katsuhiro Tamura, Osamu Shido, Masaru Kunitomo
    Abstract:

    The effect of nicorandil, an ATP-sensitive K(+) channel opener, on the level of intracellular Ca(2+) ([Ca(2+)](i)) and on ATP release in endothelial cells of the rat Caudal Artery was examined using a fluorescent confocal microscopic imaging system and high-performance liquid chromatography (HPLC) with fluorescent detection, respectively. Nicorandil significantly increased [Ca(2+)](i) and the overflow of ATP and its metabolites. The former reaction was abolished in the absence of extracellular Ca(2+), but it did not change in the presence of thapsigargin or cyclopiazonic acid. The increase in the overflow of ATP and [Ca(2+)](i) induced by nicorandil was markedly suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. The increase of [Ca(2+)](i) induced by nicorandil was significantly and inversely correlated with the level of intracellular ATP in the endothelial cells, suggesting that activation of ATP-sensitive K(+) channels by nicorandil increases Ca(2+) influx in endothelial cells. The increase of [Ca(2+)](i) might be associated with ATP release.

  • Both extracellular ATP and shear stress regulate the release of nitric oxide in rat Caudal Artery.
    Clinical and experimental pharmacology & physiology, 1999
    Co-Authors: Young Mi Kwon, Kazumasa Shinozuka, Satomi Kagota, Yu Yamaguchi, Kazuki Nakamura, Masaru Kunitomo
    Abstract:

    1. To elucidate the physiological role of nitric oxide (NO) in regulating vascular tone, the effects of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, on the vasoconstrictor response to noradrenaline (NA) in rat Caudal Artery was examined. 2. NG-Nitro-L-arginine methyl ester significantly potentiated the NA-induced increase in perfusion pressure in the perfused Caudal Artery, but did not affect the NA-induced contraction in Caudal Artery ring preparations. In addition, an increase in perfusion pressure mechanically produced by a stepwise increase in flow rate was not affected by L-NAME. 3. Noradrenaline evoked a significant increase in the release of endogenous ATP and its metabolites from the perfused Artery, whereas increased perfusion pressure as a result of increased flow rate did not evoke release of endogenous ATP. 4. In the presence of exogenously applied ATP, L-NAME significantly potentiated the increase in perfusion pressure produced by increased flow rate. 5. These results indicate that perfused vascular tone is regulated by endogenous NO and suggest that extracellular ATP may participate in the synthesis and release of NO by shear stress in endothelial cells in the rat Caudal Artery.

  • Determination of ATP and Its Metabolites Released from Rat Caudal Artery by Isocratic Ion-Pair Reversed-Phase High-Performance Liquid Chromatography
    Analytical biochemistry, 1998
    Co-Authors: Yoko Kawamoto, Kazumasa Shinozuka, Masaru Kunitomo, Jun Haginaka
    Abstract:

    A sensitive and selective assay method for adenine compounds (purines) using high-performance liquid chromatography with fluorescent detection was developed. The 1,N6-ethenoderivatives of adenine, adenosine, AMP, ADP, and ATP formed by reaction with chloroacetaldehyde at 80 degreesC were separated by ion-pair reversed-phase chromatography within 15 min under isocratic conditions. alpha,beta-Methylene adenosine 5'-diphosphate could be used as an internal standard for the determination of purines. The calibration graphs constructed with peak area ratios against amounts were linear between 0.1 and 10.0 pmol of each purine. The repeatability and intermediate precision were less than 6% (RSD, n = 5) and 8% (RSD, n = 3), respectively, at 0.5 pmol of each purine. A method for calculation of each purine amount which considers hydrolysis by derivatization is described. The optimized method was applied to determine the purines released from the rat Caudal Artery stimulated by noradrenaline.

  • Long-term supplementation with a high cholesterol diet decreases the release of ATP from the Caudal Artery in aged rats
    Life sciences, 1998
    Co-Authors: Michio Hashimoto, Young Mi Kwon, Kazumasa Shinozuka, Masaru Kunitomo, Yoko Tanabe, Hossain Md Shahdat, Shuji Gamoh, Yasuakira Tanaka, Sumio Masumura
    Abstract:

    We examined the effects of high cholesterol (HC) diet on the spontaneous and noradrenaline-induced release of ATP, ADP, AMP and adenosine from Caudal arteries and on the plasma levels of these adenyl purines in aged (100-week-old) Wistar rats. Administration of this diet for 12 weeks significantly reduced spontaneous and noradrenaline (1 micromol/L)-evoked release of adenyl purines from the Caudal arteries relative to rats given the control diet The unsaturation index of fatty acids (UI), which gives the average number of double bonds, of both the plasma and the Caudal Artery was significantly less in the HC diet-fed rats than in those fed the control diet. The HC diet for 12 weeks produced a slight but significant increase in systolic and diastolic blood pressure with advancing age. Regression analysis revealed a significant inverse relationship between the total amount of purines released from the Artery and diastolic blood pressure, and also a positive relationship between the total amount of purines released and the UI of the Caudal Artery. These results suggest that the high cholesterol diet decreased the release of adenyl purines from the Caudal arteries of aged rats, leading to an increase in blood pressure.

  • Effect of methoxamine on noradrenaline release in the Caudal Artery of hypertensive rats.
    Clinical and experimental pharmacology & physiology. Supplement, 1995
    Co-Authors: Kazumasa Shinozuka, David P. Westfall, R A Bjur, Masaru Kunitomo, Keisuke Hattori
    Abstract:

    Summary 1. The effect of methoxamine, an α1-adrenoceptor agonist, on the overflow of endogenous noradrenaline (NA) was examined in the electrically field stimulated (EFS) Caudal Artery obtained from Wistar rats, Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). 2. Methoxamine inhibited the EFS-evoked release of endogenous NA in the arteries from Wistar rats and WKY, but not in the arteries of SHR. 2-chloroadenosine, a purinoceptor agonist, also inhibited the NA release in the arteries from normotensive rats but not in the arteries of SHR. 3. The inhibitory effect of methoxamine was blocked by adenosine deaminase and potentiated by adenosine uptake inhibitor, dipyridamole. 4. Methoxamine caused the release of adenine nucleotides and adenosine from the Caudal arteries of WKY and SHR. 5. These suggest that the inhibitory effect of methoxamine on NA release is mediated by endogenous adenyl purines and that the failure of methoxamine to inhibit NA release in the Caudal Artery of SHR is due to a dysfunction of the pre-junctional purinoceptors on sympathetic nerve terminals.

Keisuke Hattori - One of the best experts on this subject based on the ideXlab platform.

  • Source of ATP, ADP, AMP and Adenosine Released from Isolated Rat Caudal Artery Exposed to Noradrenaline
    Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi, 1997
    Co-Authors: Michio Hashimoto, David P. Westfall, R A Bjur, Kazumasa Shinozuka, Keisuke Hattori, Yasuakira Tanaka, Masaaki Honda, Yukisato Ishida, Sumio Masumura
    Abstract:

    Purines of ATP, ADP, AMP and adenosine released from rat Caudal Artery with and without endothelium and the isolated smooth muscle and endothelial cells were examined, in order to determine the source. Treatment of intact segments of Caudal arteries with noradrenaline (10μM) for 3min induced a large release of ATP, ADP, AMP and adenosine.However, if the Artery segments had been denuded of their endothelial lining, noradrenaline induced only a slight release of purines. Endothelial cells in primary culture prepared from Caudal arteries, when exposed to noradrenaline for 3min released large amounts of purines, whereas vascular smooth muscle cells prepared similarly and passaged endothelial cells did not release purines upon exposure to noradrenaline. These results indicate that, of smooth muscle and endothelial cells of the vascular wall, only intact endothelial cells react to α adrenoceptorstimulation by releasing adenine nucleotides and adenosine.

  • The effects of age on the release of adenine nucleosides and nucleotides from rat Caudal Artery.
    The Journal of Physiology, 1995
    Co-Authors: M. Hashimoto, David P. Westfall, R A Bjur, Kazumasa Shinozuka, Keisuke Hattori, Sumio Masumura
    Abstract:

    1. The spontaneous and alpha-adrenoceptor-induced release of ATP, ADP, AMP and adenosine were determined from arterial segments and from isolated endothelial cells from Caudal arteries of young (5-week-old), adult (30-week-old) and old (100- to 110-week-old) Wistar rats. 2. The spontaneous (non-evoked) release of the sum total of the four purines was significantly greater from Artery segments of young rats than from adult and old rats. 3. The release of the adenine nucleotides and adenosine induced by methoxamine (10 microM), an alpha 1-adrenoceptor agonist, was greater from Artery segments from young rats than from old rats. 4. The spontaneous release of the sum total of the four purines was significantly greater from endothelial cells prepared from Caudal arteries of young rats than of old rats. 5. The noradrenaline (10 microM)-induced release of the sum total of the four purines was significantly greater from endothelial cells prepared from Caudal arteries of young rats than of old rats. 6. The levels of adenine nucleotides and adenosine, determined in plasma from anaesthetized rats, were significantly higher in young rats compared with adult and old rats. 7. These findings suggest that the release of ATP from the vascular endothelial cells is reduced with advancing age.

  • Effect of methoxamine on noradrenaline release in the Caudal Artery of hypertensive rats.
    Clinical and experimental pharmacology & physiology. Supplement, 1995
    Co-Authors: Kazumasa Shinozuka, David P. Westfall, R A Bjur, Masaru Kunitomo, Keisuke Hattori
    Abstract:

    Summary 1. The effect of methoxamine, an α1-adrenoceptor agonist, on the overflow of endogenous noradrenaline (NA) was examined in the electrically field stimulated (EFS) Caudal Artery obtained from Wistar rats, Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). 2. Methoxamine inhibited the EFS-evoked release of endogenous NA in the arteries from Wistar rats and WKY, but not in the arteries of SHR. 2-chloroadenosine, a purinoceptor agonist, also inhibited the NA release in the arteries from normotensive rats but not in the arteries of SHR. 3. The inhibitory effect of methoxamine was blocked by adenosine deaminase and potentiated by adenosine uptake inhibitor, dipyridamole. 4. Methoxamine caused the release of adenine nucleotides and adenosine from the Caudal arteries of WKY and SHR. 5. These suggest that the inhibitory effect of methoxamine on NA release is mediated by endogenous adenyl purines and that the failure of methoxamine to inhibit NA release in the Caudal Artery of SHR is due to a dysfunction of the pre-junctional purinoceptors on sympathetic nerve terminals.

  • Release of endogenous ATP from the Caudal Artery in rats with arteriosclerosis.
    European journal of pharmacology, 1994
    Co-Authors: Kazumasa Shinozuka, Yu Yamaguchi, Masaru Kunitomo, Yoko Tanabe, Satomi Kitagawa, Motohatsu Fujiwara, Keisuke Hattori
    Abstract:

    Abstract Noradrenaline significantly increased (by a prazosin-sensitive mechanism) the overflow of ATP and its metabolites from the Caudal arteries of rats treated with excess vitamin D 2 and a high-cholesterol diet (arteriosclerotic rats), although the amount of the overflow was smaller than that in the normal rats. The arteries from the arteriosclerotic rats showed a marked increase in the calcium content and there was a significant negative correlation between the noradrenaline-induced overflow of ATP and the arterial calcium content. These findings indicate that ATP release from arteriosclerotic rat Caudal arteries mediated by α 1 -adrenoceptors is impaired in proportion to the extent of arterial calcification.