Modulation by bradykinin and nitric oxide of angiotensin II-induced apoptosis in a vascular smooth muscle cell phenotype.
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.
Colie
S
S
U858, Cardiac and Renal Department, Institut Médecine Moléculaire Rangueil I2MR, INSERM, Toulouse, F-31432, France.
Pecher
C
C
Girolami
J P
JP
Blaes
N
N
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar
D000804:Angiotensin II; D009599:Nitroprusside; D009569:Nitric Oxide; D001920:Bradykinin