Up-regulated neuronal nitric oxide synthase compensates coronary flow response to bradykinin in endothelial nitric oxide synthase-deficient mice

M. A.Hassan Talukder, Takako Fujiki, Keiko Morikawa, Minako Motoishi, Hiroshi Kubota, Tsuyoshi Morishita, Masato Tsutsui, Akira Takeshita, Hiroaki Shimokawa

研究成果: Article査読

28 被引用数 (Scopus)

抄録

It has been reported that endothelium-dependent relaxations are preserved in isolated coronary arteries of endothelial nitric oxide synthase-deficient (eNOS-/-) mice with a possible involvement of nNOS. However, it remains to be examined whether nNOS compensates coronary flow response in a beating heart of eNOS-/- mice and if so, whether and where nNOS is up-regulated. Coronary flow response to bradykinin was examined in Langendorff-perfused hearts from WT and eNOS-/- mice. Bradykinin-induced coronary flow was greater in eNOS-/- mice than in WT mice, and indomethacin had no inhibitory effect on it. Bradykinin receptor antagonist HOE-140 abolished the bradykinin response in both strains. Nonselective NOSs inhibitor L-NNA inhibited the bradykinin-induced coronary flow in both strains, whereas specific inhibitors of nNOS, SMTC, and 7-NI, significantly attenuated the coronary flow response only in eNOS-/- mice. A guanylate cyclase inhibitor ODQ also attenuated the bradykinin response in eNOS-/- mice. Immunohistochemistry revealed the presence of nNOS mainly in coronary vascular smooth muscle cells (VSMCs) in both strains and Western blot analysis demonstrated a marked increase in cardiac nNOS expression in eNOS-/- mice. These results indicate that nNOS compensates coronary flow response to bradykinin in eNOS-/- mice, for which upregulation of nNOS in VSMCs may be involved.

本文言語English
ページ(範囲)437-445
ページ数9
ジャーナルJournal of cardiovascular pharmacology
44
4
DOI
出版ステータスPublished - 2004 10月

ASJC Scopus subject areas

  • 薬理学
  • 循環器および心血管医学

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