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1989 Fiscal Year Final Research Report Summary

An approach to understand the pathogenesis of coronary artery spasm by molecular and cellular biology techniques

Research Project

Project/Area Number 63570396
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionKobe University School of Medicine

Principal Investigator

YOKOYAMA Mitsuhiro  Kobe University School of Medicine Associate Professor, 医学部, 助教授 (40135794)

Co-Investigator(Kenkyū-buntansha) KAWAHARA Yasuhiro  Kobe University School of Medicine Assistant Professor, 医学部, 助手 (80169755)
AKITA Hozuka  Kobe University School of Medicine Assistant Professor, 医学部, 助手 (60175792)
Project Period (FY) 1988 – 1989
KeywordsSerotonin / Histamine / Vascular smooth muscle cell / Vascular endothelium / Low density lipoprotein / Endothelium-derived relaxing factor / Lysophosphatidylcholine / Atrial natriuretic peptide
Research Abstract

We obtained the following results in these 2 years.
(1) Contraction and Phosphoinositides(PI) turnover were studied in atherosclerotic(AS) and control(C) rabbit aortas. Stimulation with 5-HT in AS exhibited augmented contraction and PI labeling compared with C, although NE-induced contraction and PI labeling were identical in both groups. These results indicate that 5-HT-mediated hypercontraction and signal transduction abnormality were present in atherosclerotic arteries.
(2) Effects of endothelium-derived relaxing factor(EDRF) on histamine(HA)-induced vasocsustriction and PI turnover were studied in rabbit thoracic aorta. HA exhibited contraction and [^<32>P]Pi incorporation into PI. Removal of the endothelium and methylene blue potentiate the contraction and PI labeling induced by HA. These results suggest that PI turnover and contraction in response to HA were regulated by the negative feedback EDRF.
(3) The inhibitory effects of native low density lipoprotein(LDL) and modified LDL wi … More th copper oxidation and phospholipase A_2(PLA_2) on endothelium-dependent relaxation(EDR) were examined in rabbit thoracic aorta. Native LDL had no effects on ACh-induced EDR, whereas PLA_2 treated LDL and oxidized LDL inhibited EDR. Furthermore, exogeneous administration of synthetic LPC had a potent inhibitory action on EDR. These results indicate that LPC is the principal substance for the inhibitory effect of oxidized LDL.
(4) Lysophospholipase activity was measured in rabbit aorta. The enzyme did not require Ca^<2+> for its activation. Cholesterol inhibited the lysophospholipase activity. These results may imply the importance of the lysophospholipase activity inhibition by cholesterol as the responsible mechanisms for the enhanced accumulation of LPC in atherosclerotic vessels.
(5) The vasodilatory response to human arterial natriuretic peptide(hANP) were compared between normal and atherosclerotic(AS) rabbit aortas. The hANP-induced relaxation and cyclic GMP formation in AS were markedly reduced. These results suggest that hANP-induced vasodilating response through membrane-bound guanylate cyclase system is impaired in AS arteries. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] R.Miyake,M.Yokoyama,H.Fukuzaki: "Inhibition of Lysophospholipase by Cholesterol in Rabbit Aorla" Biochemical and Biophysical Research Communications.167. 143-147 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Yokoyama,K.Hirata,R.Miyake,H.Akita,Y.Ishikawa,H.Fukuzaki: "LYSOPHOSPHATIDYLCHOLINE:ESSENTIAL ROLE IN THE INHIBITION OF ENDOTHELIUM-DEPENDENT VASORELAXATION BY OXIDIZED LOW DENSITY LIPOPROTEIN" Biochemical and Biophysical Research Communications. (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Nishimoto,M.Yokoyama,H.Fukuzaki: "Self-suppression of phosphoinositides tumover and contraction by stimulating the release of endogenous endotheliumderived relaxing factor in vascular action of histamine." Cardiovascular Research.24. (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Ichikawa,M.Yokoyama,H.Akita,H.Fukuzaki: "Constriction of a Large Coronary Artery Contributes to Serotonin-Induced Myocardial Ischemia in the Dog With Pliable Coronary Stenosis." Joumal of the American College of Cardiology.14. 449-459 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Awano,M.Yokoyama,H.Fukuzaki: "Role of Serotonin,Histamine and Thromboxane A2 in Platelet-Induced Contractions of Coronary Arteries and Aortae From Rabbits." Joumal of Cardiovascular Pharmacology. 13. 781-792 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Go,M.Yokoyama,H.Akita,H.Fukuzaki: "PHORBOL ESTER MODULATES SEROTONINSTIMULATED PHOSPHOINOSTTIDE BREAKDOWN IN CULTURED VASCULAR SMOOTH MUSCLE CELL" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 153. 51-58 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Miyake, M.Yokoyama, H.Fukuzaki: "Inhibition of Lysophospholipase by Cholesterol in Rabbit Aorta" Biochemical and Biophysical Research Communications. 167. 143-147 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Yokoyama, K.Hirata, R.Miyake, H.Akita, Y.Ishikawa, H.Fukuzaki: "LYSOPHOSPHATIDYLCHOLINE: ESSENTIAL ROLE IN THE INHIBITION OF ENDOTHELIUM-DEPENDENT VASORELAXATION BY OXIDIZED LOW DENSITY LIPOPROTEIN" Biochemical and Biophysical Research Communications 1990.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Nishimoto, M.Yokoyama, H.Fukuzaki: "Self-suppression of phosphoinositides tumover and contraction by stimulating the release of endogenous endotheliumderived relaxing factor in vascular action of histamine" Cardiovascular Research 24 1990.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Ichikawa, M.Yokoyama, H.Akita, H.Fukuzaki: "Constriction of a Large Coronary Artcry Contributes to Serotonin-Induced Myocardial Ischemia in the Dog With Pliable Coronary Stenosis" Journal of the American College of Cardiology 14 449-459 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Awano, M.Yokoyama, H.Fukuzaki: "Role of Serotonin, Histamine and Thromboxane A2 in Platelet-Induced Contractions of Coronary Arteries and Aortae From Rabbits" Journal of Cardiovascular Pharmacology 13 781-792 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Go, M.Yokoyama, H.Akita, H.Fukuzaki: "PHORBOL ESTER MODULATES SEROTONIN-STIMULATED PHOSPHOINOSITIDE BREAKDOWN IN CULTURED VASCULAR SMOOTH MUSCLE CELL" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 153 51-58 1988.

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

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Published: 1993-03-26  

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