1996 Fiscal Year Annual Research Report

冠動脈の緊張亢進や内膜肥厚の防止に関する細胞分子生物学的研究

Research Project

Project/Area Number	07407022
Research Category	Grant-in-Aid for Scientific Research (A)
Research Institution	Kyushu University
Principal Investigator	金出英夫九州大学, 医学部, 教授 (80038851)
Co-Investigator(Kenkyū-buntansha)	西村淳二九州大学, 医学部, 助教授 (90237727) 小林誠九州大学, 医学部, 助教授 (80225515)
Keywords	冠動脈攣縮 / 内膜肥厚 / 血管平滑筋 / 冠血管形成術 / 細胞周期 / 細胞増殖 / 細胞情報伝達
Research Abstract	本研究は、冠動脈平滑筋細胞の緊張・増殖の制御とその破綻の機序、およびその防止法を細胞分子生物学的に明らかにすることを目的とする。前年度に開発した「細胞内イオン変化の連続・二次元測定システム」とReverse transcription polymerase chain rection(RTPCR)法を用いて。以下の研究成果を得た。 (1)ラット大動脈内膜擦過モデルにRTPCR法を応用し、大動脈にはRho A mRNAが擦過後早期から発現すること、これは内膜肥厚や平滑筋細胞の増殖よりも以前に起きることを明らかにした。 (2)big endothelin(ET)1は[Ca^<2+>]i上昇をともなって豚冠動脈を収縮させた。これはET転換酵素(ECE)阻害剤の前処置により抑制された。豚冠動脈平滑筋にはpreproET-1、preproET-3、ET_A、ET_B受容体、ECE-1のmRNA発現が証明された。ETは冠循環においてオートクリン型の血管緊張制御を行うことが示唆された。 (3)豚腎動脈には、α_<1A>およびα_<1B>受容体が存在することを、薬理学的反応およびRTPCR法を用いて証明した。α_<1A>受容体は細胞外Ca^<2+>の流入、α_<1B>受容体は細胞内Ca^<2+>の放出に関与することを明らかにした。 (4)in situ 豚大動脈弁内皮細胞では、ATP、bradykinin、thrombin、ionomycinの何れもが用量依存性に[Ca^<2+>]i上昇とNO産生増加を引き起こす。同じ程度の[Ca^<2+>]i上昇であってもNO産生量はアゴニスト毎に異なることが明らかとなった。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] H.Jahan: "Endothelin 1 and angiotensin II act as progression but not competence growth factors in vascular smooth muscle cells." Eur J Pharmacol. 295. 261-269 (1996)
[Publications] S.Abe: "Some effects of nipradilol,a β-blocker possessing a nitroxy group,on smooth muscle of the pig coronary artery." Br J Pharmacol. 117. 1707-1715 (1996)
[Publications] H.Seguchi: "The mechanism of relaxation induced by atrial natriuretic peptide in the porcine renal artery" Br J Pharmacol. 118. 343-351 (1996)
[Publications] Y.Miyagi: "Dual regulation of cerebrovascular tone by UTP:P_<2U> receptor-mediated contraction and endothelium-dependennt relaxation." Br J Pharmacol. 118. 847-856 (1996)
[Publications] C.Sakihara: "Expression of calponin mRNA in porcine aortic endothelial cells." Biochem Biophys Res Commun. 222. 195-200 (1996)
[Publications] Y.Miyagi: "P_<2U> purinergic activation leads to the cell cycle progression from the G_1 to the S and M phases but not the G_0 to G_1 phase in vascular smooth muscle cells in primary culture." Biochem Biophys Res Commun. 222. 652-658 (1996)
[Publications] Y.Miyagi: "P_<2U> receptor is linked to cytosolic Ca^<2+> transient and release of of vasorelaxing factorin bovine endothelial cells in situ." J Physiol. 492.3. 751-761 (1996)
[Publications] Y.Fukuizumi: "The effects of calcitonin gene-related peptide on the cytosolic calcium concentration and force in the porcine coronary artery." J Pharmacol Exp Ther. 278. 220-231 (1996)
[Publications] Y.Higuchi: "CPA induces a sustained increase in(Ca^<2+>)i of endothelial cells in situ and relaxes porcine coronary artery." Am J Physiol. 270. H2038-H2049 (1996)
[Publications] T.Kuga: "Cell cycle-dependent expression of L- and T-type Ca^<2+> currents in vascular smooth muscle cells." Circ Res. 79. 14-19 (1996)
[Publications] C.Sakihara: "The direct inhibitory effect of chlorpromazineon smooth muscle of the porcine pulmonary atery." Anesthesiology. 85. 616-625 (1996)
[Publications] J.Nishimura: "Expression of rhoA and rho kinase mRNAs in porcine vascular smooth muscle." Biochem Biophys Res Commun. 227. 750-754 (1996)
[Publications] T.Kai: "Halothane counteracts acetylcholine-induced increase in Ca^<2+> sensitivity of the contractile apparatus in air way smooth muscle." Eur J Pharmacol22GD13:315. 313-318 (1996)
[Publications] X.Chem: "Resting load modulates the myofilament Ca^<2+> -sensitivity in rabbit cerebral arteries." J Cereb Blood Flow Metab. (in press).
[Publications] G.Hiroshi: "The differential effects of diltiazem and nitroglycerin on cytosolic Ca concentration and on force in the bovine opthalmic artery." Invest Ophthalmolol Vis Sci. (in press).
[Publications] J.Nishimura: "Adrenomedullin relaxes particular smooth muscles despite a general expression of its mRNA smooth muscle,endothelial and epithelial cells21GC16:Br J Pharmacol" (in press).
[Publications] D.Eguchi: "Mechanism of contraction induced by bradykinin in the rabbit saphenous vein." Br J Pharmacol. (in press).
[Publications] N.Niiro: "Up-regulation of RHO A and RHO-kinase mRNA in the rat myometrium during pregnancy." Biochem Biophys Res Commun. (in press).

1996 Fiscal Year Annual Research Report

冠動脈の緊張亢進や内膜肥厚の防止に関する細胞分子生物学的研究

Principal Investigator

金出 英夫 九州大学, 医学部, 教授 (80038851)

Research Products

[Publications] H.Jahan: "Endothelin 1 and angiotensin II act as progression but not competence growth factors in vascular smooth muscle cells." Eur J Pharmacol. 295. 261-269 (1996)

[Publications] S.Abe: "Some effects of nipradilol,a β-blocker possessing a nitroxy group,on smooth muscle of the pig coronary artery." Br J Pharmacol. 117. 1707-1715 (1996)

[Publications] H.Seguchi: "The mechanism of relaxation induced by atrial natriuretic peptide in the porcine renal artery" Br J Pharmacol. 118. 343-351 (1996)

[Publications] Y.Miyagi: "Dual regulation of cerebrovascular tone by UTP:P_<2U> receptor-mediated contraction and endothelium-dependennt relaxation." Br J Pharmacol. 118. 847-856 (1996)

[Publications] C.Sakihara: "Expression of calponin mRNA in porcine aortic endothelial cells." Biochem Biophys Res Commun. 222. 195-200 (1996)

[Publications] Y.Miyagi: "P_<2U> purinergic activation leads to the cell cycle progression from the G_1 to the S and M phases but not the G_0 to G_1 phase in vascular smooth muscle cells in primary culture." Biochem Biophys Res Commun. 222. 652-658 (1996)

[Publications] Y.Miyagi: "P_<2U> receptor is linked to cytosolic Ca^<2+> transient and release of of vasorelaxing factorin bovine endothelial cells in situ." J Physiol. 492.3. 751-761 (1996)

[Publications] Y.Fukuizumi: "The effects of calcitonin gene-related peptide on the cytosolic calcium concentration and force in the porcine coronary artery." J Pharmacol Exp Ther. 278. 220-231 (1996)

[Publications] Y.Higuchi: "CPA induces a sustained increase in(Ca^<2+>)i of endothelial cells in situ and relaxes porcine coronary artery." Am J Physiol. 270. H2038-H2049 (1996)

[Publications] T.Kuga: "Cell cycle-dependent expression of L- and T-type Ca^<2+> currents in vascular smooth muscle cells." Circ Res. 79. 14-19 (1996)

[Publications] C.Sakihara: "The direct inhibitory effect of chlorpromazineon smooth muscle of the porcine pulmonary atery." Anesthesiology. 85. 616-625 (1996)

[Publications] J.Nishimura: "Expression of rhoA and rho kinase mRNAs in porcine vascular smooth muscle." Biochem Biophys Res Commun. 227. 750-754 (1996)

[Publications] T.Kai: "Halothane counteracts acetylcholine-induced increase in Ca^<2+> sensitivity of the contractile apparatus in air way smooth muscle." Eur J Pharmacol22GD13:315. 313-318 (1996)

[Publications] X.Chem: "Resting load modulates the myofilament Ca^<2+> -sensitivity in rabbit cerebral arteries." J Cereb Blood Flow Metab. (in press).

[Publications] G.Hiroshi: "The differential effects of diltiazem and nitroglycerin on cytosolic Ca concentration and on force in the bovine opthalmic artery." Invest Ophthalmolol Vis Sci. (in press).

[Publications] J.Nishimura: "Adrenomedullin relaxes particular smooth muscles despite a general expression of its mRNA smooth muscle,endothelial and epithelial cells21GC16:Br J Pharmacol" (in press).

[Publications] D.Eguchi: "Mechanism of contraction induced by bradykinin in the rabbit saphenous vein." Br J Pharmacol. (in press).

[Publications] N.Niiro: "Up-regulation of RHO A and RHO-kinase mRNA in the rat myometrium during pregnancy." Biochem Biophys Res Commun. (in press).

金出英夫九州大学, 医学部, 教授 (80038851)