Positive Inotropic, Negative Chronotropic, and Coronary Vasoconstrictor Effects of Acetylcholine in Isolated Rat Hearts : Role of Muscarinic Receptors, Prostaglandins, Protein Kinase C, Influx of Extracellular Ca^<2+>, Intracellular Ca^<2+> Release, and Endothelium

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The involvement of nitric oxide (NO), muscarinic receptors, prostaglandins, calcium influx via slow calcium channels, Ca<SUP>2+</SUP> release from intracellular stores, protein kinase C, and endothelium in the positive inotropic, negative chronotropic, and coronary vasoconstrictor effects of acetylcholine (ACh) has been investigated in isolated rat hearts. The perfusion of hearts with ACh (10<SUP>-7</SUP>, 5×10<SUP>-7</SUP>, and 10<SUP>-6</SUP> M) produced marked decreases in heart rate and coronary flow and a marked increase in contractile force. Similar effects have been observed during the perfusion of hearts with ACh in the presence of N<SUP>ω</SUP>-nitro-L-arginine methyl ester (L-NAME), which is an inhibitor of NO synthesis. The positive inotropic, negative chronotropic, and coronary vasoconstrictor effects of ACh were abolished by muscarinic receptor blocker atropine. In hearts pretreated with cyclooxygenase inhibitor indomethacin, ACh significantly decreased heart rate but did not significantly affect coronary flow and contractile force. In the presence of calcium channel antagonist verapamil or protein kinase C inhibitor staurosporine, ACh produced a significant drop in heart rate but did not significantly affect coronary perfusion pressure and force of contraction. In the presence of the inhibitor of the release of Ca<SUP>2+</SUP> from intracellular stores dantrolene sodium, ACh produced a significant increase in coronary perfusion pressure and a marked decline in heart rate, but did not significantly affect force of contraction. Furthermore, the disruption of endothelium by perfusing the hearts with saponin abolished the vasoconstrictor effect of ACh but did not alter negative chronotropic and positive inotropic effect. Our results suggest that ACh causes vasoconstrictor, negative chronotropic, and positive inotropic effects in isolated rat hearts. Cardiac effects of ACh are related to muscarinic receptor activation, and prostaglandins modulate ACh-induced vasoconstriction and positive inotropy. Our data also suggest that protein kinase C and calcium influx from extracellular source may be responsible for the vasoconstrictor and positive inotropic effect of ACh. The calcium release from intracellular stores may mediate the positive inotropic effect, and the vasoconstrictor effect of ACh depends on an intact endothelium.

収録刊行物

  • The Japanese journal of physiology

    The Japanese journal of physiology 48(6), 483-491, 1998-12-01

    PHYSIOLOGICAL SOCIETY OF JAPAN

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各種コード

  • NII論文ID(NAID)
    10008305955
  • NII書誌ID(NCID)
    AA00691224
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    0021521X
  • NDL 記事登録ID
    4652965
  • NDL 雑誌分類
    ZS8(科学技術--医学--解剖学・生理学・生化学)
  • NDL 請求記号
    Z53-D40
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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