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1996 Fiscal Year Final Research Report Summary

Control of vascular tone by endothelium-derived relaxing and hyperpolarizing factors

Research Project

Project/Area Number 07670786
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

NAKAYA Yutaka  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (50136222)

Co-Investigator(Kenkyū-buntansha) NAKAYA Yutaka  The University of Tokushima, School of Medicine, Professor (50136222)
Project Period (FY) 1995 – 1996
Keywordsartery / endothelium / vascular smooth muscle cells / nitric oxide / endothelium-derived relaxing factor / patch clamp
Research Abstract

Control of vascular tone by endothelium-derived relaxing (EDRF) and hyperpolarizing factors (EDHF) was studied in cultured porcine coronary artery smooth muscle cells and endothelial cells using patch clamp techniques. We characterized two major K channels in smooth muscle cells, i.e.ATP sensitive K channel (KATP) and Ca^<2+>-activated K channels (Kca) and studied the target channels for EDRF and EDHF.These channels were targets organs of various vasoactive substances as well, and many vasoactive aubstances exert their actions through thses channels.
In cell-attached patches, EDRF,which is known as nitric oxide (NO), activated Kca channel of smooth muscle cells via production of cGMP.We also found that NO also activated KATP channels and hyperpolarized membrane. In inside-out patches NO did not activated thses channels. We also studied the effect of EDHF on the ionic channles of smooth muslce cells, where is located close to the coronary artery strips with intact endothelium. In the pre … More sence of N^G-monomethyl L-arginine (LNMMA) and indomethacine, acetylcholine activated Kca channels of smooth muscle, suggesting that the target of EDHF was Kca channels. Tetraethylammonium and charybdotoxin, specific Kca channel blockers, suppressed this channels but glibenclamide, a specific KATP channel blocker, did not significantly altered the channel activity.
We also found new pathway for production of NO from endothelium of porcine coronary artery and aorta. Different from previous studies, histamine did not increased cytosolic Ca^<2+> in endothelium but increased cAMP in endothelium. Histamine produced NO in the presence of histamine H_1 receptor antagonist, but NO production was significantly suppressed in the presence of H_2 receptor antagonist, suggesting that the histamine-induced NO production was mediated by H_2 receptor and through cAMP production. Amrinone, a phosphodiesterase inhibitor, and folskoline, an activator of adenylate cyclase, produced NO from porcine endothelium. These results indicated that there in a new pathway of NO production and that NO is produced by increasing cAMP without increase in cytosolic Ca^<2+>. Less

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Hirokazu Miyoshi: "Endotoxin-induced nonendothelial nitric oxide activates the Ca^+ activated K^+ channel in cultured vascular smooth muscle cells" J Mol Cell Cardiol. 26. 1487-1495 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirokazu Miyoshi: "Nonendothelial-derived nitric oxide activates the K^<2+> channels in cultured vascular smooth muscle cells" Heart Vessels. Suppl.9. 109-111 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirokazu Miyoshi: "Calcitonin gene-related peptide activates the K^+ channels of vascular smooth muscle cells via adenvlate cyclase" Basic Res Cardiol. 90. 332-336 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazushi Minami: "Protein kinase C-independent inhibition of the Ca^<2+>-activated K^+ channel by angiotensin II and endthelin I" Biochemical Pharmacology. 49. 1051-1056 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fumiko Kishi: "Intracellular ΔandΔextracellular Ca^<2+> regulate histmaine-induced release of nitric oxide in vascular endothelial cells as shown with sensitive and selective nitric oxide electrodes" Pharmacological Research. 33. 123-126 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhiro Mori: "Endothelium-dependent relaxation of rat thoracic aorta by amrinone-induced nitric oxide release" European Heart Journal. 17. 308-316 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yutaka Nakaya: "Central nervous system and blood pressure control" Cyclic AMP-mediated nitric oxide production by vasoactive substances, 9 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yutaka Nakaya: "Smooth muscle excitation" ATP-sensitive potassium channels in vascular smooth muscle cells, 12 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kudo M ; Nakaya Y ; Matsuoka S ; Saito K ; Kuroda Y: "Atrial natriuretic factor and isosorbide dinitrate modulate the gating of ATP-sensitive K+ channels in cultured vascular smooth muscle cells." Circ Res. 74 (3). 471-6 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi H ; Nakaya Y ; Moritoki H: "Nonendothelial-derived nitric oxide activates the ATP-sensitive K+ channel of vascular smooth muscle cells." FEBS Lett.345 (1). 47-9 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Martin DK ; Nakaya Y ; Wyse KR ; Campbell TJ: "Effects of disopyramide and flecainide on the kinetics of inward rectifier potassium channels in rabbit heart muscle." Br J Pharmacol. 111 (3). 873-9 (1994)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Hamada Y ; Nakaya Y ; Hamada S ; Kamada M: "Aono Teur Activation of K+ channels by ritodrine hydrochloride in uterine smooth muscle cells from pregnant women." Eur J Pharmacol. 288 (1). 45-51 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi H ; Nakaya Y: "Endotoxin-induced nonendothelial nitric oxide activates the Ca (2+)-activated K+ channel in cultured vascular smooth muscle cells." J Mol Cell Cardiol. 26 (11). 1487-95 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Minami K ; Hirata Y ; Tokumura A ; Nakaya Y ; Fukuzawa K: "Protein kinase C-independent inhibition of the Ca (2+)-activated K+ channel by angiotensin II and endothelin-1." Biochem Pharmacol. 49 (8). 1051-6 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi H ; Nakaya Y: "Calcitonin gene-related peptide activates the K+ channels of vascular smooth muscle cells via adenylate cyclase." Basic Res Cardiol. 90 (4). 332-6 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi H ; Kishi F ; Watanabe K ; Nomura M ; Saito K,Nakaya Y: "Nonendothelial-derived nitric oxide activates the K+ channels in cultured vascular smooth muscle cells." Heart Vessels. Suppl.9. 109-111 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nameda Y ; Miyoshi H ; Tsuchiya K ; Nakaya Y ; Arase S: "Endotoxin-induced L-arginine pathway produces nitric oxide and modulates the Ca2+-activated K+ channel in cultured human dermal papilla cells." J Invest Dermatol. 106 (2). 342-5 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi H ; Nakaya Y ; Saito K ; Kishi F ; Takakura M ; Nomura M: "MCI-154 activates the Ca (2+)-activated K+ channel of vascular smooth muscle cells." Life Sci.56 (15). PL291-8 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakaya Y ; Yamamoto S ; Hamada Y ; Kamada M ; Aono T ; Niwa M: "Inducible nitric oxide synthase in uterine smooth muscle." Life Sci.58 (13). PL249-55 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kishi F ; Nakaya Y ; Takahashi A ; Miyoshi H ; Nomura M ; Saito K: "Intracellular and extracellular Ca^<2+> regulate histamine-induced release of nitric oxide in vascular endothelial cells as shown with sensitive and selective nitric oxide electrodes." Pharmacelogical Research. 33 (2). 123-126 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori K ; Takeuchi S ; Moritoki H ; Tsuchiya K ; Nakaya Y Matsuoka S ; Kuroda Y: "Endothelium-dependent relaxation of rat thoracic aorta by amrinone-induced nitric oxide release." Eur Heart J. 17 (2). 308-16 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakaya Y ; Miyoshi H: ATP-sensitive potassium channels in vascular smooth muscle cells."Smooth Muscle Excitation" edited by TB Bolton and T Tomita, 97-108 Academic Press (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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