Hypotensive Interaction of Sildenafil and Nicorandil in Rats Through the cGMP Pathway but Not by K_<ATP> Channel Activation

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Abstract

The possibility that sildenafil citrate can potentiate nicorandil-induced hypotension by increasing cGMP levels of vascular smooth muscle cells was examined using anesthetized rats and isolated aortas. In pentobarbital-anesthetized rats, more than 0.3mg/kg of sildenafil (i.v.) potentiated intra-aortic (i.Ao.) administration of nitroglycerin-induced hypotension. Hypotension due to nicorandil (100μg/kg, i.Ao.) was potentiated by sildenafil (1mg/kg, i.v.), even after glibenclamide treatment, although pinacidil-induced hypotension was not reinforced. Hypotensive responses to neither nitroglycerin (3μg/kg, i.v.) nor nicorandil (100μg/kg, i.v.) were potentiated by sildenafil, however. Increases in femoral blood flow due to nitroglycerin (0.1-3μg, i.a.) were potentiated significantly by sildenafil, but those due to nicorandil (1-30μg, i.a.) were not. Isolated rat aortas precontracted with phenylephrine were dilated dose-dependently using nicorandil, nitroglycerin, pinacidil or sildenafil. The relaxant effect due to nicorandil and nitroglycerin was reinforced significantly by pretreatment with an ineffective concentration of sildenafil (10<SUP>-8</SUP>M), but pinacidil was not. After ODQ (1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxalin-1-one) completely blocked relaxation by nicorandil, sildenafil did not increase relaxation. These findings suggest that combination of sildenafil with nicorandil, as well as with nitroglycerin, potentiates the hypotensive response by augmentation of vasodilatation. Synergism of vasodilation may be linked with NO action, but not with K<SUB>ATP</SUB> channel-activation.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 84(3), 316-324, 2000-11-01

    The Japanese Pharmacological Society

References:  35

Cited by:  3

Codes

  • NII Article ID (NAID)
    10008186257
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    5586947
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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