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

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)437-445
Number of pages9
JournalJournal of cardiovascular pharmacology
Volume44
Issue number4
DOIs
Publication statusPublished - 2004 Oct

Keywords

  • Bradykinin
  • Coronary flow
  • Nitric oxide
  • Nitric oxide synthases

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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