Role of bradykinin-NO pathway in prevention of cardiac hypertrophy by ACE inhibitor in rat cardiomyocytes.
To examine whether the bradykinin-nitric oxide (NO) pathway directly participates in the antihypertrophic property of angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure, the effects of bradykinin were studied in rat cultured heart cells. Bradykinin (0.1, 1 nM) prevented the phenylephrine-induced increase in protein/DNA content, an index of hypertrophy of heart cells, and amplified the nitrite/nitrate content in the medium. Perindoprilat (1 microM), an ACE inhibitor, also restrained the progression of cardiac hypertrophy and augmented NO release. These effects of perindoprilat were abolished by HOE-140 (kinin B2 antagonist), N omega-nitro-L-arginine (NO synthase inhibitor), and methylene blue (guanylate cyclase inhibitor). Furthermore, there was a significant correlation between protein/DNA content and nitrite/nitrate content. These results indicate that bradykinin inhibits the progression of cardiac hypertrophy due to the increase in NO release and that perindoprilat produces beneficial effects on cardiac hypertrophy by stimulating the bradykinin-NO pathway.
Ishigai
Y
Y
New Product Research Laboratories II, Tokyo Research and Development Center, Daiichi Pharmaceutical Company, Japan.
Mori
T
T
Ikeda
T
T
Fukuzawa
A
A
Shibano
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D065168:Bradykinin Receptor Antagonists; D006332:Cardiomegaly / Q000517:prevention & control*; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000502:physiology; D012044:Regression Analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D007211:Indoles; D009566:Nitrates; D009573:Nitrites; D018002:Receptors, Bradykinin; D010656:Phenylephrine; D019335:Nitroarginine; C053500:perindoprilat; D009569:Nitric Oxide; C065679:icatibant; D001920:Bradykinin