Endothelial dysfunction limits the antihypertrophic action of bradykinin in not cardiomyocytes

We have previously demonstrated that bradykinin blocks hypertrophy of isola ted cardiomyocytes: this is dependent on the release of nitric oxide from e ndothelial cells. In the present study, we investigated the influence of en dothelial dysfunction on the antihypertrophic action of bradykinin. Angiote nsin II (1 mu M) induced a 34 +/- 2% increase in [H-3]phenylalanine incorpo ration (P<0.001), an in vitro marker of hypertrophy, in adult rat cardiomyo cytes co-cultured with bovine aortic endothelial cells. This response was b locked by bradykinin (10 mu M), but restored by the nitric oxide synthase i nhibitor, N-omega-monomethyl-L-arginine (100 mu M). However, the antihypert rophic effect of bradykinin in co-culture was abolished by 24h pretreatment of endothelial cells with high glucose (25 mM, to mimic hyperglycemia) and attenuated by hydrogen peroxide (100 mu M, to mimic oxidative stress). Pre treatment with oxidized low-density lipoprotein (100 mu g/ml for 24 h, to m imic hyperlipidemia) was without effect. The hypertrophic response to angio tensin II was not modified by endothelial cell pretreatment. Furthermore, t he ability of bradykinin to elevate cGMP (a marker for nitric oxide) in car diomyocytes co-cultured with endothelial cells was attenuated by pretreatme nt with either high glucose or hydrogen peroxide, In conclusion, loss of th e cardioprotective action of bradykinin against angiotensin II-induced hype rtrophy was associated with impaired nitric oxide release from dysfunctiona l endothelial cells. (C) 2000 Academic Press.