Modulation by bradykinin and nitric oxide of angiotensin II-induced apoptosis in a vascular smooth muscle cell phenotype

• Published in: International immunopharmacology 2008-02, Vol.8 (2), p.231-236
• Main Authors: Colie, S., Pecher, C., Girolami, J.P., Blaes, N.
• Format: Article
• Language: English
• Subjects: Angiotensin II; Angiotensin II - pharmacology; Animals; Apoptosis; Apoptosis - drug effects; Bradykinin; Bradykinin - pharmacology; Cell Survival; Cell Survival - drug effects; KKS; Muscle, Smooth, Vascular; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Nitric Oxide; Nitric Oxide - physiology; Nitroprusside; Nitroprusside - pharmacology; Phenotype; RAS; Rats; Rats, Wistar; Survival; VSMC
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2007.09.006

There is evidence for a clinical benefit of ACE inhibitors or AT1 antagonists in cardiovascular diseases with deleterious smooth muscle cells (SMC) apoptosis. We have previously shown that angiotensin II (Ang II) induces a phenotype-dependent SMC apoptosis. We asked whether bradykinin (BK) and nitric oxide (NO) could modulate Ang II-induced SMC apoptosis. BK alone did not induce significant apoptosis in either spindle (Sp-SMC) or epithelioid (Ep-SMC) SMC phenotypes cultured in serum reduction, but phenotype-dependently, reduced cell proliferation. Pretreatment with BK partly impaired Ang II-induced reduction of Ep-SMC culture viability and partly prevented apoptotic features. Pretreatment with sodium nitroprusside completely prevented all Ang II-induced deleterious effects in Ep-SMC, i. e. reduction of culture viability, Annexin V binding, nuclear condensation and cell fragmentation. These findings indicate that the BK–NO system may phenotype-dependently modulate SMC survival and in particular may oppose, mostly by NO, Ang II-induction of apoptosis in the Ep-SMC phenotype.