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 μM), 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 ω-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 eff...