Effects of a Prostaglandin I_2 Analog Iloprost on Cytoplasmic Ca^<2+> Levels and Muscle Contraction in Isolated Guinea Pig Aorta

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Author(s)

    • OZAKI Hiroshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
    • ABE Asaki
    • Department of Animal Science and Technology, Faculty of Agriculture, Okayama University
    • UEHIGASHI Yusuke
    • Department of Animal Science and Technology, Faculty of Agriculture, Okayama University
    • KINOSHITA Masayoshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
    • HORI Masatoshi
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
    • MITSUI-SAITO Minori
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo
    • KARAKI Hideaki
    • Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo

Abstract

In the isolated guinea pig aorta, the prostaglandin 12 analog iloprost (0.01-10 μM) inhibited the contractions induced by the thromboxane A<SUB>2</SUB> analog U46619 (9, 11-dideoxy-llα, 9α-epoxymethanoprostaglandin F<SUB>2α</SUB>; 30 nM) and prostaglandin F<SUB>2α</SUB> (PGF<SUB>2α</SUB>, 1 μM) in a concentration-dependent manner. In contrast, iloprost only partially inhibited the high K<SUP>+</SUP> (65.4 mM)-induced contraction. In the muscle stimulated with high K<SUP>+</SUP>, verapamil (0.3 and 10 μM)inhibited [Ca<SUP>2+</SUP>]<SUB>i</SUB> and muscle tension in parallel, whereas iloprost (1 μM) inhibited muscle tension with only a small decrease in [Ca<SUP>2+</SUP>]<SUB>i</SUB>. In the muscle stimulated with U46619 (30 nM), verapamil and iloprost decreased both [Ca<SUP>2+</SUP>]<SUB>i</SUB> and muscle tension. However, as compared with the effect of verapamil, iloprost more strongly inhibited muscle tension than [Ca<SUP>2+</SUP>]<SUB>i</SUB>. The iloprost (0.1—1 μM)-induced relaxation was accompanied by a concentration-dependent increase in cAMP content. It was further demonstrated that inhibition of the U46619-contractions was augmented in the presence of cycloxygenase inhibitors, such as indomethacin (10 μM), ibuprofen (10 μM) and aspirin (10 μM). In contrast, the inhibition of PGF<SUB>2α</SUB>-induced contraction was not affected by indomethacin. Similarly, the inhibitory effect of forskolin on U46619-induced contractions, but not on PGF<SUB>2α</SUB>-induced contraction, was enhanced by indomethacin. These results suggest that iloprost inhibits vascular smooth muscle contraction by decreasing [Ca<SUP>2+</SUP>]<SUB>i</SUB> and the Ca<SUP>2+</SUP> sensitivity of contractile elements through a cAMP-dependent mechanism. The results also suggest that in U46619-stimulated muscle, vasoactive prostaglandins that counterbalance the relaxing action of cAMP may be generated.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 71(3), 231-237, 1996-07

    The Japanese Pharmacological Society

References:  24

Cited by:  3

Codes

  • NII Article ID (NAID)
    10008188989
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • Data Source
    CJP  CJPref  J-STAGE 
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